Low-fat Meal Research Articles

Plasma stearoyl-CoA desaturase activity indices and bile acid concentrations after a low-fat meal: association with a genetic variant in the FTO gene.

PurposeDietary macronutrient composition, stearoyl-CoA desaturase (SCD) activity indices, and primary bile acid (BA) concentrations are among the factors that have been associated with lipid metabolism and contributed to obesity. We investigated the association between the polymorphic expression of the fat mass and obesity-associated (FTO) gene and its relationship with SCD activity indices and primary BA concentrations after a low-fat meal.Subjects and methodsBlood plasma samples were collected from 56 young (20–36 years) healthy subjects with different rs9939609 FTO genotypes. Fasting and post-meal (2 hours after a low-fat breakfast) blood samples were collected on the subsequent morning for the analysis of DNA methylation, SCD activity indices (product-to-precursor fatty acid ratios; 16:1n-7/16:0 and 18:1n-9/18:0), and chenodeoxycholic acid (CDCA) and cholic acid (CA) concentrations. Expression of lipogenic genes was investigated post-meal to assess the relationship between the CDCA and CA concentrations and mRNA levels of lipogenic genes.ResultsThe FTO AA (obesity risk) genotype group (n=18) had higher (P<0.05) post-meal SCD-16 activity index than the FTO TT (wild type) genotype group (n=26). In both the FTO TT (n=16) and AA (n=8) genotype groups, the post-meal concentrations of CDCA and CA were lower (P<0.05) compared with the fasted state. No difference in BA concentrations between the FTO TT and AA genotype groups in both meal states was observed. After adjusting for the body mass index, the highest 50% post-meal concentrations of CA were inversely (P=0.010) correlated with the level of mRNA SCD expression.ConclusionFTO AA carriers may be at a higher risk for obesity through higher SCD activity in a low-fat diet environment. This effect may be partly pronounced by very low CA concentrations.

Maternal Postprandial Triglycerides in the Home Setting

Background and Aims: Elevated maternal triglycerides (TG) have been associated with adverse pregnancy outcomes including an increased risk of preeclampsia and macrosomia. Maternal TG are primarily measured in the fasting state and at single time points during pregnancy. Temporal and prandial changes in TG levels during pregnancy are not well described. The purpose of this study was to examine flux of capillary glucose and TG in late pregnancy, how they are influenced by high and low fat meals, and whether they relate to infant body composition. Materials and Methods: Women in the third trimester of pregnancy completed 4 days of home capillary glucose and TG monitoring (4 times a day (fasting and two hours post each meal)). Using the Roche Accutrend Plus meter. Each woman consumed an isocaloric high fat (41%) and a low fat (25%) breakfast meal on different days during the study period. Area under the curve (AUC) for the capillary glucose and TG measures after the standardized meals was calculated using trapezoidal approximation. AUC for women with and without GDM was compared for each meal and metabolic measure. Infant body fat % was measured by air displacement plethysmography. Results: To date, thirteen women, 7 with GDM and 6 normoglycaemic have completed the study. Median capillary glucose levels: fasting 5.0 (95% CI 4.6-5.2) mmol/L and postprandial 6.0 (95% CI 5.7-6.2) mmol/L. Median capillary TG: fasting 3.3 (95% CI 2.9-3.8) mmol/L and postprandial 3.6 (95% CI 3.2-3.8) mmol/L. Mean infant body fat % 10.6 (SD4.9)%. There were no significant differences in capillary glucose or triglycerides between the meals although capillary glucose trended higher with the low fat meal. GDM status did not affect the AUC glucose or AUC triglycerides for either meal. Conclusion: This study demonstrates that capillary triglycerides can be monitored at home in a similar fashion to capillary glucose. Capillary triglyceride levels were not related to infant anthropometry and did not vary significantly with meal fat content. Recruitment is ongoing. Disclosure H.L. Barrett: None. M. Dekker: Speaker's Bureau; Self; Abbott. Other Relationship; Self; Nestlé. S.J. de Jersey: None. M.C. d'Emden: Advisory Panel; Self; AstraZeneca. Speaker's Bureau; Self; AstraZeneca. Advisory Panel; Self; Eli Lilly and Company. Speaker's Bureau; Self; Eli Lilly and Company, Boehringer Ingelheim GmbH. Advisory Panel; Self; Sanofi. Speaker's Bureau; Self; Sanofi, Novo Nordisk A/S, Novartis Pharmaceuticals Corporation. L. Callaway: None. H. McIntyre: Speaker's Bureau; Self; Novo Nordisk Inc.. Research Support; Self; Danish Diabetes Academy.

Meal composition influences postprandial sensations independently of valence and gustation.

Palatability of meals with identical composition has been shown to influence postprandial sensations. Our aim was to determine to what extent meal composition influences postprandial sensations independently of palatability. Randomized, crossover, double-blind trial comparing the postprandial responses to a low-fat vs a high-fat test meal, with the same physical and organoleptic characteristics (taste, smell, texture, color, and temperature). The test meal consisted in 150g hummus containing either 17.7g fat (low-fat) or 22.3g fat (high-fat), 19.8g toasts, 120mL water and 50g apple puree. In 12 non-obese healthy men, palatability, homeostatic sensations (hunger/satiety, fullness) and hedonic sensations (digestive well-being, mood) were measured on 10cm scales before and during the 60-min postprandial period. Comparisons between meals were performed with a two-way repeated measures ANCOVA with premeal data as co-variate. Both test meals were rated equally palatable (palatability scores 3.8±0.3 low-fat, 3.3±0.2 high-fat; P=.156). As compared to the high-fat meal, the low-fat meal induced more satisfaction (meal effect on well-being F(1,21)=4.92; P=.038) and tended to improve mood (meal effect F(1,21)=3.02; P=.064), and this was associated with a non-significant decrease in satiety (meal effect F(1,21)=2.29; P=.145) and fullness (meal effect F(1,21)=1.57; P=.224). The composition of meals with equal palatability influences postprandial satisfaction, even without significant impact on homeostatic sensations, although an effect on homeostatic sensations has not been excluded. These conditioning factors may have clinical implications in patients with impaired meal tolerance or meal-related symptoms.

Pazopanib with low fat meal (PALM) in advanced renal cell carcinoma (RCC).

683 Background: Pazopanib, a highly lipophilic standard first-line therapy for metastatic RCC, is conventionally taken in a fasting state but has significant gastrointestinal toxicities and 96% of ingested drug is fecally excreted, with major financial implications. Single dose studies with fat meals suggested bioavailability is increased two-fold. We sought to evaluate toxicity/safety, bioavailability and anti-tumor efficacy of daily pazopanib taken with a low fat meal over 12 weeks. Methods: Enrolled pts had unresectable locally advanced or metastatic RCC with clear cell component, RECIST 1.1 measurable disease, ECOG PS ≤2, adequate organ function, and up to 3 prior therapies including VEGF(R) and checkpoint inhibitors. Subjects took pazopanib, starting dose of 400 mg, once daily with low-fat meal ( &lt; 400 cal with &lt; 20% fat/10 g of fat) in 2 wk cycles with MD discretion to dose-escalate q2wks up to 800 mg or irreversibly dose-reduce as low as 200 mg based on tolerance/toxicity for 12 wks. Baseline and end of study echocardiograms, and triplicate ECGs at each cycle start were monitored. Home pill diaries were collected. PK was analyzed in the first 3 cycles. Results: Sixteen pts were accrued: median age 60 (range: 47 – 75),75% men,11 were ECOG PS 0. Most (12/16) subjects with no prior therapy, 13/16 had intermittent Heng risk criteria, 3 favorable; 5 sarcomatoid component. Diet compliance by pill diary was outstanding, except for 1 pt for 1 cycle. Calculated mean daily dose was 535 mg (153-750 mg). Therapy was well tolerated; 5 Grade 3 AEs (1 HTN, 1 chest pain, 2 AST/ALT elevations, 1 Abd pain) occurred. LVEF declined by &gt; 15% in 3 pts but none to &lt; 50%. QTc prolongation &gt; 450 ms did not occur. All but 3 pts completed protocol (off d/t toxicity-HTN, LFTs, chest pain). ORR was PR 5 (31%); SD 7 (44%). PK data and pharmacogenomics CYP3A4 polymorphism data correlated with toxicity. Conclusions: Pazopanib taken with a low fat meal appears to be better tolerated compared to published data on empty stomach administration, especially with fewer GI toxicities, including diarrhea. It also resulted in comparable efficacy with fewer cumulative pills over the 12-week period, with substantial cost implications. Larger trials of pazopanib with low fat meal are warranted. Clinical trial information: NCT02729194.

The acute effects on duodenal gene expression in healthy men following consumption of a low-fat meal enriched with theobromine or fat

Increasing apoA-I synthesis may improve HDL functionality and lower CVD risk. As theobromine and fat increase fasting apoA-I concentrations, and the intestine is involved in apoA-I production, the acute effects of both were studied on duodenal gene transcription to better understand underlying mechanisms. In this crossover study, 8 healthy men received once a low fat (LF) meal, a LF meal plus theobromine (850 mg), or a high fat (HF) meal. Five hours after meal intake duodenal biopsies were taken for microarray analysis. Theobromine and HF consumption did not change duodenal apoA-I expression. Theobromine did not change gene expression related to lipid and cholesterol metabolism, whereas those related to glycogen/glucose breakdown were downregulated. HF consumption increased gene expression related to lipid and cholesterol uptake and transport, and to glucose storage, while it decreased those related to glucose uptake. Furthermore, genes related to inflammation were upregulated, but inflammation markers in plasma were not changed. In healthy men, acute theobromine and fat consumption did not change duodenal apoA-I mRNA, but inhibited expression of genes related to glucose metabolism. Furthermore, HF intake activated in the duodenum expression of genes related to lipid and cholesterol metabolism and to inflammation.

Effects of posaconazole (a strong CYP3A4 inhibitor), two new tablet formulations, and food on the pharmacokinetics of idasanutlin, an MDM2 antagonist, in patients with advanced solid tumors.

Idasanutlin, a selective small-molecule MDM2 antagonist in phase 3 testing for refractory/relapsed AML, is a non-genotoxic oral p53 activator. To optimize its dosing conditions, a number of clinical pharmacology characteristics were examined in this multi-center trial in patients with advanced solid tumors. This was an open-label, single-dose, crossover clinical pharmacology study investigating the effects of strong CYP3A4 inhibition with posaconazole (Part1), two new oral formulations (Part2), as well as high-energy/high-fat and low-energy/low-fat meals (Part3) on the relative bioavailability of idasanutlin. After completing Part 1, 2, or 3, patients could have participated in an optional treatment with idasanutlin. Clinical endpoints were pharmacokinetics (PK), pharmacodynamics (PD) of MIC-1 elevation (Part1 only), and safety/tolerability. The administration of posaconazole 400mg BID × 7days with idasanutlin 800mg resulted in a slight decrease (7%) in Cmax and a modest increase (31%) in AUC for idasanutlin, a marked reduction in Cmax (~ 60%) and AUC0 (~ 50%) for M4 metabolite, and a minimal increase (~ 24%) in serum MIC-1 levels. Cmax and AUC were both 45% higher for the SDP formulation. While the low-fat meal caused a less than 20% increase in all PK exposure parameters with the 90% CI values just outside the upper end of the equivalence criteria (80-125%), the high-fat meal reached bioequivalence with dosing under fasting. In patients with solid tumors, multiple doses of posaconazole, a strong CYP3A4 inhibitor, minimally affected idasanutlin PK and PD without clinical significance. The SDP formulation improved rBA/exposures by ~ 50% without major food effect.

OA 05.07 Efficacy and Updated Safety of Ceritinib (450 Mg or 600 Mg) with Low-Fat Meal vs 750 Mg Fasted in ALK+ Metastatic NSCLC

OA 05.07 Efficacy and Updated Safety of Ceritinib (450 Mg or 600 Mg) with Low-Fat Meal vs 750 Mg Fasted in ALK+ Metastatic NSCLC

Identification of the principal transcriptional regulators for low-fat and high-fat meal responsive genes in small intestine

BackgroundHigh-fat (HF) diet is a well-known cause of obesity. To identify principle transcriptional regulators that could be therapeutic targets of obesity, we investigated transcriptomic modulation in the duodenal mucosa following low-fat (LF) and HF meal ingestion.MethodsWhereas one group of mice was sacrificed after fasting, the others were fed ad libitum with LF or HF meal, and sacrificed 30 min, 1 h and 3 h after the beginning of the meal. A transcriptome analysis of the duodenal mucosa of the 7 groups was conducted using both microarray and serial analysis of gene expression (SAGE) method followed by an Ingenuity Pathways Analysis (IPA).ResultsSAGE and microarray showed that the modulation of a total of 896 transcripts in the duodenal mucosa after LF and/or HF meal, compared to the fasting condition. The IPA identified lipid metabolism, molecular transport, and small molecule biochemistry as top three molecular and cellular functions for the HF-responsive, HF-specific, HF-delay, and LF-HF different genes. Moreover, the top transcriptional regulator for the HF-responsive and HF-specific genes was peroxisome proliferator-activated receptor alpha (PPARα). On the other hand, the LF-responsive and LF-specific genes were related to carbohydrate metabolism, cellular function and maintenance, and cell death/cellular growth and proliferation, and the top transcriptional regulators were forkhead box protein O1 (FOXO1) and cAMP response element binding protein 1 (CREB1), respectively.ConclusionsThese results will help to understand the molecular mechanisms of intestinal response after LF and HF ingestions, and contribute to identify therapeutic targets for obesity and obesity-related diseases.

ASCEND-8: A Randomized Phase 1 Study of Ceritinib, 450 mg or 600 mg, Taken with a Low-Fat Meal versus 750 mg in Fasted State in Patients with Anaplastic Lymphoma Kinase (ALK)-Rearranged Metastatic Non–Small Cell Lung Cancer (NSCLC)

IntroductionCeritinib, 750 mg fasted, is approved for treatment of patients with ALK receptor tyrosine kinase gene (ALK)-rearranged (ALK-positive) NSCLC previously treated with crizotinib. Part 1 of the ASCEND-8 study determined whether administering ceritinib, 450 mg or 600 mg, with a low-fat meal may enhance gastrointestinal (GI) tolerability versus 750 mg fasted in patients with ALK-positive NSCLC while maintaining similar exposure. MethodsASCEND-8 is a multicenter, randomized, open-label, phase 1 study. Part 1 investigated the steady-state pharmacokinetics (PK) and safety of ceritinib, 450 mg or 600 mg, taken with a low-fat meal versus 750 mg fasted in patients with advanced ALK-positive NSCLC who were either treatment naive or pretreated with chemotherapy and/or crizotinib. Part 2 will assess efficacy and safety of ceritinib in treatment-naive patients. ResultsAs of June 16, 2016, 137 patients were randomized (450 mg fed [n = 44], 600 mg fed [n = 47], and 750 mg fasted [n = 46]); 135 patients received ceritinib. Median follow-up duration was 4.14 months. At steady state, relative to 750 mg fasted, 450 mg with food demonstrated comparable PK as assessed by maximum (peak) concentration of drug in plasma and area under the plasma concentration–time curve from time zero to 24 hours, whereas 600 mg with food demonstrated approximately 25% higher PK. Relative to 750 mg fasted, 450 mg with food was associated with a lower proportion of patients with GI toxicities, mostly grade 1 (diarrhea [43.2%], nausea [29.5%], and vomiting [18.2%]); there were no grade 3 or 4 events, study drug discontinuations, or serious AEs due to GI toxicities. ConclusionCeritinib, 450 mg with food, had similar exposure and a more favorable GI safety profile than ceritinib, 750 mg in fasted patients with ALK-positive NSCLC.

Effect of Food on Abiraterone Pharmacokinetics: A Review

Recent reports suggest a potentially beneficial increase in abiraterone exposure when abiraterone acetate plus prednisone is administered with food. We evaluated the basis for current dosing recommendations under modified fasted conditions for patients with metastatic castration-resistant prostate cancer with a PubMed search of studies assessing the impact of food on abiraterone pharmacokinetics. Studies show that abiraterone exposure increases with administration in a fed versus fasted state and with high-fat versus low-fat meals. Food effect is substantially attenuated in metastatic castration-resistant prostate cancer patients compared with healthy subjects. The potential variability in absorption, unproven clinical benefits and increased toxicity with abiraterone acetate plus prednisone administration in the fed state underscore the importance of adhering to current dosing recommendations.

Ceritinib plus nivolumab (NIVO) in patients (pts) with anaplastic lymphoma kinase positive (ALK+) advanced non-small cell lung cancer (NSCLC).

2502 Background: Induction of PD-L1 expression due to constitutive oncogenic signaling has been reported in NSCLC models harboring EML4–ALK rearrangements. Here we explore whether the combination of ALKi (ceritinib) and PD1-inhibitor (NIVO) will provide sustained clinical benefit to pts with ALK+ NSCLC. Methods: This phase 1 dose escalation study enrolled previously treated (ALK inhibitor [ALKi] or chemotherapy) or tx-naive pts with stage IIIB/IV ALK+ NSCLC; who received NIVO 3 mg/kg IV Q2W + ceritinib with low-fat meal, at 450 mg/day (group 1) or 300 mg/day (group 2) until progression/unacceptable toxicity. Primary objective: MTD/recommended dose for expansion. Dose escalation was guided by Bayesian logistic regression model with overdose control. Results: Median follow-up: group 1 (n = 14) 13 mos (10-15); group 2 (n = 22) 6 mos (2-10). As of 9 Sep 2016, 16/36 (44%) pts discontinued tx: disease progression (11 [31%] pts), AE’s (3 [8%] pts), and death (2 [6%] pts). In group 1, 4 pts experienced DLT: pancreatitis (n = 2), lipase and transaminase increase (n = 1), and autoimmune hepatitis (n = 1). In group 2, 2 pts experienced DLT: G3 ALT increase. Both dose levels met Bayesian criteria for dose expansion. Overall most frequent (≥40%) AEs (n = 36), were diarrhea (64%), ALT increase (56%), AST increase (44%) and vomiting (42%). Most frequent ( &gt; 10%) grade ≥3 AEs were increases in ALT (22%), GGT (17%), amylase (11%), and lipase (11%), and maculopapular rash (11%). Incidence of rash (grouped term) was 61%; similar in both groups. Grade 3 rash was reported in 29% pts in group 1 and 14% pts in group 2. Preliminary ceritinib steady state PK (AUC0-24 and Cmax) suggested that 300 mg/day exposure was ~ 70-75% of 450 mg/day. Confirmed (c)/unconfirmed (u) ORR: ALKi-pretreated pts (group 1 [n = 8], group 2 [n = 12]) was 63% (4 cPR,1 uPR; 95% CI: 25%, 92%), and 33% (4 uPR) 95% CI: 10%, 65%) respectively; ALKi-naïve pts, (group 1 [n = 6], group 2 [n = 10]) was 83% (5 cPR; 95% CI: 36%, 100%), and 70% (1 cCR, 3 cPR 3uPR; 95% CI: 35%, 93%) respectively. Conclusions: Ceritinib + NIVO is an active combination in ALK+ NSCLC. However, the protocol will be amended to address observed toxicities. Data will be updated for presentation. Clinical trial information: NCT02393625.

What to eat and drink in the festive season: a pan-European, observational, cross-sectional study.

Digestive discomfort after meals is common in the community, especially during the festive season. It is uncertain whether this is related to intake of either high-calorie or high-fat foods or, alternatively, intake of specific foods. This prospective, cross-sectional study tested the hypothesis that the risk of reflux or dyspepsia is associated with the fat content of the meal independent of caloric load in a 'real-life' setting. Four festive meals were served to delegates attending a conference on four consecutive days. Test meals had the same volume, but varied in calorie and fat content. Study procedures and symptoms were monitored using a mobile application (SymTrack). The effect of alcoholic compared with nonalcoholic drinks was also assessed. Primary outcome was the occurrence of reflux or dyspeptic symptoms. Fullness was documented by a visual analogue scale. A total of 84/120 (70%) delegates aged 22-69 years consented to participate. At screening, 22 (31%) participants reported at least mild symptoms on the Leuven Dyspepsia Questionnaire. Specific ingredients did not appear to impact on postprandial symptoms. All high-calorie dinners [British, German, Italian (with alcohol)] induced more symptoms than the low-fat, low-calorie Czech dinner [odds ratio: 2.6, 95% confidence interval (CI): 0.97-6.9 (P=0.058), 1.5 (0.3-3.8), and 2.8 (0.7-10.5), respectively]. Self-reported fullness after the high-fat, high-calorie British dinner was higher by 23/100 (95% CI: 4-42, P=0.016) with respect to low-fat, low-calorie Czech and German dinners. Study participants tolerated a range of food and drink well. Reflux or dyspeptic symptoms were least likely after the low-fat, low-calorie meal. Fullness was increased after the high-fat, high-calorie dinner, but not low-fat meals. These results will help the public to make evidence-based dietary choices during the carnival season!

Treatment Patterns and Early Outcomes of ALK-Positive Non-Small Cell Lung Cancer Patients Receiving Ceritinib: A Chart Review Study.

This study aimed to provide the first real-world description of the characteristics, treatments, dosing patterns, and early outcomes of patients with ALK-positive non-small cell lung cancer (NSCLC) who received ceritinib in US clinical practice. US oncologists provided data from medical charts of adult patients diagnosed with locally advanced or metastatic ALK-positive NSCLC who received ceritinib following crizotinib. Patient characteristics, treatment patterns, ceritinib dosing, early outcomes, and occurrence of gastrointestinal adverse events (AEs) by dose and instructions on food intake were assessed, and Kaplan-Meier analysis was used to describe clinician-defined progression-free survival (PFS) on ceritinib. Medical charts of 58 ALK-positive NSCLC patients treated with ceritinib were reviewed (median age 63years; 41% male; 21% with prior chemotherapy experience). At ceritinib initiation, 44 patients had multiple distant metastases, most commonly in the liver (60%), bone (53%), and brain (38%). Initial ceritinib dose varied: 71% received 750mg, 19% 600mg, and 10% 450mg. Although median follow-up after ceritinib initiation was short (3.8months), most patients achieved either a complete or partial response (69%) on ceritinib, regardless of metastatic sites present at initiation or initial dose. Median PFS on ceritinib was 12.9months. 17% of patients had a gastrointestinal AE reported during follow-up. The majority of events occurred in patients instructed to fast; no patients instructed to take a lower dose of ceritinib with food reported gastrointestinal AEs. These early findings of ceritinib use in clinical practice suggest that ceritinib is effective at treating crizotinib-experienced ALK-positive NSCLC patients, regardless of metastatic sites or initial dose, and dosing ceritinib with food may lead to fewer gastrointestinal AEs. Future studies with larger sample size and longer follow-up are warranted, including an ongoing randomized trial to assess the gastrointestinal tolerability of ceritinib 450 and 600mg with low-fat meals. Novartis Pharmaceutical Corporation.

Food Effect on Oral Bioavailability: Old and New Questions.

Food Effect on Oral Bioavailability: Old and New Questions.

The Impact of Avocado Fruit on Postprandial Satiety: an Acute Dose Response Study

Avocado fruit contains a unique combination of monounsaturated fat and dietary fibers. Previous studies have tested the effects of fat or fiber on satiety/appetite control; however data are limited on the interaction of fat and fiber to enhance satiety. The aim of the present study was to characterize the effect of avocados, a fruit naturally high in healthy fat and dietary fiber, on subjective and biological indicators of satiety. Thirty‐one adults who were overweight or obese (body mass index 29.0 ± 2.4 kg/m2, age 37.9 ± 10.3 y, n = 16 female and n = 15 male) participated in this 3‐arm, single‐blinded, cross‐over clinical trial. Participants were provided a low fat high carbohydrate breakfast control meal (CON) or two energy‐matched meals containing either half an avocado (HA, 68 g) or a whole avocado (WA, 136 g) on 3 different occasions at least one week apart. Blood samples were collected at baseline (0 h) and 0.5, 1, 2, 3, 4, and 6 h after treatment to assess changes in glucagon‐like peptide‐17‐36 (GLP‐1), peptide YY3‐36 (PYY) and total ghrelin. Visual analog scales (VAS) were used to measure changes in subjective satiety (hunger, fullness, desire to eat, and prospective consumption) and mood variables during the same 6 h time frame. Area under the curve analysis indicated the WA meal increased GLP‐1 by 17% and PYY by 21% compared to the CON meal, p &lt; 0.05, whereas ghrelin was suppressed 25% more after the CON meal compared to WA meal, p &lt; 0.05. Assessment of motivation to eat and mood variables indicated a significant reduction in prospective consumption after the WA and HA meals compared to CON meal, p ≤ 0.05 and increased fullness after WA meal compared to HA (P&lt;0.05), but not compared to CON (p=0.11). The study results indicate that increasing the fat and fiber content of a breakfast meal with avocados compared to an iso‐energetic low fat meal increased feelings of fullness and reduced the amount of food subjects wanted to eat over 6 h. These data are consistent with an elevation in two known satiety peptides (GLP‐1 and PYY) and suggest that avocados may have an important role in helping individuals manage the amount they want to eat between meals and possibly at the next meal.Support or Funding InformationSupported by Hass Avocado Board, Irvine, CA

An additional bolus of rapid-acting insulin to normalise postprandial cardiovascular risk factors following a high-carbohydrate high-fat meal in patients with type 1 diabetes: A randomised controlled trial.

To evaluate an additional rapid-acting insulin bolus on postprandial lipaemia, inflammation and pro-coagulation following high-carbohydrate high-fat feeding in people with type 1 diabetes. A total of 10 males with type 1 diabetes [HbA1c 52.5 ± 5.9 mmol/mol (7.0% ± 0.5%)] underwent three conditions: (1) a low-fat (LF) meal with normal bolus insulin, (2), a high-fat (HF) meal with normal bolus insulin and (3) a high-fat meal with normal bolus insulin with an additional 30% insulin bolus administered 3-h post-meal (HFA). Meals had identical carbohydrate and protein content and bolus insulin dose determined by carbohydrate-counting. Blood was sampled periodically for 6-h post-meal and analysed for triglyceride, non-esterified-fatty acids, apolipoprotein B48, glucagon, tumour necrosis factor alpha, fibrinogen, human tissue factor activity and plasminogen activator inhibitor-1. Continuous glucose monitoring captured interstitial glucose responses. Triglyceride concentrations following LF remained similar to baseline, whereas triglyceride levels following HF were significantly greater throughout the 6-h observation period. The additional insulin bolus (HFA) normalised triglyceride similarly to low fat 3-6 h following the meal. HF was associated with late postprandial elevations in tumour necrosis factor alpha, whereas LF and HFA was not. Fibrinogen, plasminogen activator inhibitor-1 and tissue factor pathway levels were similar between conditions. Additional bolus insulin 3 h following a high-carbohydrate high-fat meal prevents late rises in postprandial triglycerides and tumour necrosis factor alpha, thus improving cardiovascular risk profile.

Increasing the protein quantity in a meal results in dose-dependent effects on postprandial glucose levels in individuals with Type 1 diabetes mellitus.

To determine the glycaemic impact of increasing protein quantities when consumed with consistent amounts of carbohydrate in individuals with Type 1 diabetes on intensive insulin therapy. Participants with Type 1 diabetes [aged 10-40 years, HbA1c ≤ 64 mmol/mol (8%), BMI ≤ 91st percentile] received a 30-g carbohydrate (negligible fat) test drink daily over 5 days in randomized order. Protein (whey isolate 0 g/kg carbohydrate, 0 g/kg lipid) was added in amounts of 0 (control), 12.5, 25, 50 and 75 g. A standardized dose of insulin was given for the carbohydrate. Postprandial glycaemia was assessed by 5 h of continuous glucose monitoring. Data were collected from 27 participants (15 male). A dose-response relationship was found with increasing amount of protein. A significant negative relationship between protein dose and mean excursion was seen at the 30- and 60-min time points (P = 0.007 and P = 0.002, respectively). No significant relationship was seen at the 90- and 120-min time points. Thereafter, the dose-response relationship inverted, such that there was a significant positive relationship for each of the 150-300-min time points (P < 0.004). Mean glycaemic excursions were significantly greater for all protein-added test drinks from 150 to 300 min (P < 0.005) with the 75-g protein load, resulting in a mean excursion that was 5 mmol/l higher when compared with the control test drink (P < 0.001). Increasing protein quantity in a low-fat meal containing consistent amounts of carbohydrate decreases glucose excursions in the early (0-60-min) postprandial period and then increases in the later postprandial period in a dose-dependent manner.

Minimal food effect for eicosapentaenoic acid and docosahexaenoic acid bioavailability from omega-3–acid ethyl esters with an Advanced Lipid TechnologiesTM (ALT®)–based formulation

The absorption of eicosapentaenoic acid (EPA; 20:5n-3) and docosahexaenoic acid (DHA; 22:6n-3) omega-3-acid ethyl esters (EEs) is influenced by food. There is a need for a formulation of EE that is less impacted by food effect. SC401 is a novel Advanced Lipid Technologies-based formulation of EPA-EE and DHA-EE. In the presence of an aqueous medium, Advanced Lipid Technologies forms stable micelles in situ independent of bile salt secretion. This effect is hypothesized to improve EPA-EE and DHA-EE bioavailability while it helps mitigate the food effect associated with their consumption. The aim of the article was to assess the effect of food on the bioavailability of DHA and EPA after a single oral dose of 1530mg omega-3 fatty acids EE (SC401) in 24 healthy subjects under fasted and low-fat (9% of total calories from fat) and high-fat (50% of total calories from fat) meal conditions. This was a randomized, open-label, single-dose, 3-period, 3-way crossover study. Blood samples for pharmacokinetic analyses were taken at predose and at 0.5, 1, 2, 3, 3.5, 4, 4.5, 5, 5.5, 6, 6.5, 7, 8, 10, 12 and 24hours postdose. To assess the safety of the intervention, active monitoring of adverse events, physical examinations, vital signs, clinical laboratory assessments (chemistry, hematology, and urinalysis), and 12-lead electrocardiograms were conducted. SC401 showed high bioavailability of both EPA and DHA in fasted, low-fat meal, and high-fat meal conditions. No differences were found in SC401 DHA AUC0-t (t=24hours) among the 3 conditions (91.69% high-fat/fasted, 97.12% low-fat/fasted, and 105.92% low-fat/high-fat; P>.05 in all cases). In contrast, SC401 EPA AUC0-t was affected by food intake (179.06% high-fat/fasted, P<.0001; 150.05% low-fat/fasted, P<.0001) and the amount of fat taken with SC401 (83.80% low-fat/high-fat; P=.0009). SC401 was safe and well tolerated. A single dose of SC401 resulted in high levels of EPA and DHA total lipids in plasma in fasting and fed conditions. SC401 overcame the food effect for DHA and partially ameliorated it for EPA. SC401 represents a convenient option for treatment of severe hypertriglyceridemia, especially for patients under a restricted intake of dietary fat.

The additional dose of insulin for high-protein mixed meal provides better glycemic control in children with type 1 diabetes on insulin pumps: randomized cross-over study.

Delivery of insulin for high-protein low-fat meals with carbohydrates on the basis of carbohydrates leads to higher late postprandial glycemia. Studies with mixed meals demonstrated lower blood glucose level after dual wave bolus. The objective of our study was to assess the impact of additional dose of insulin in dual wave bolus for high-protein mixed meal on the postprandial glycemia. We performed a randomized, double-blind, two-way cross-over study, including 58 children with type 1 diabetes, aged 14.7 ± 2.2 years. Participants were randomly assigned into two treatment orders: NORMAL-DUAL or DUAL-NORMAL BOLUS. They consumed standardized high-protein, low-fat meals with carbohydrates. The primary outcome was postprandial glycemia (PPG) based on capillary blood glucose measurements (CBGM). The secondary outcomes were the frequency of hypoglycemia, area under glucose curve, mean amplitude of glycemic excursion (MAGE) and glycemic rise. PPG assessed at 180 min was significantly lower when dual wave bolus was delivered (NORMAL 162 mg/dL [9 mmol/L] vs DUAL 130.0 mg/dL [7.22 mmol/L]; P = .004). There were no differences in CBGM between both groups at 60 and 120 min. We found differences between the groups in MAGE at 120 min (NORMAL 82.86 mg/dL [4.6 mmol/L] versus DUAL 54.76 mg/dL [3.04 mmol/L]; P = .0008). We observed no differences in the number of hypoglycemic episodes in both groups. Applying an additional dose of insulin in dual wave bolus for high-protein mixed meal improved PPG. We observed no statistically significant increase in the number of hypoglycemic episodes associated with this intervention.

P3.02a-036 Phase 1 Study of Ceritinib 450 mg or 600 mg Taken with a Low-Fat Meal versus 750 mg in Fasted State in ALK+ Metastatic NSCLC: Topic: Miscellaneous

The anaplastic lymphoma kinase (ALK) inhibitor ceritinib is approved at 750 mg fasted for the treatment of patients with ALK-rearranged (ALK+) metastatic non-small cell lung cancer (NSCLC) pretreated with crizotinib. The pharmacokinetic (PK) part of this study (Part 1) compares PK exposure of ceritinib following food consumption versus a fasted state in advanced ALK+ NSCLC patients. Part 1 of this prospective, open-label, multicenter, randomized, 3-arm, phase 1 study (ASCEND-8; NCT02299505) is investigating PK and safety of ceritinib in advanced ALK+ NSCLC patients, treatment-naïve or pretreated with multiple lines of chemotherapy and/or crizotinib. Here, we compare steady-state PK of ceritinib 450 or 600 mg taken with a low-fat meal versus ceritinib 750 mg fasted (primary endpoint) and report preliminary safety outcomes from Part 1. Part 2 continues to randomize treatment-naïve patients and will assess safety and efficacy. As of June 16, 2016 (data cut-off), 137 patients were randomized in a 1:1:1 ratio to each treatment arm; 135 patients received one dose (safety set) and 97 patients had evaluable steady-state PK data. Disease characteristics were comparable between arms. Median follow-up duration was 4.14 months (range, 0.1–13.9). Relative to 750 mg fasted, the 450 mg fed arm demonstrated comparable steady-state PK, while the 600 mg fed arm showed ∼25% higher steady-state PK (Table). Preliminary safety data suggests overall frequency of AEs and types of AEs were comparable between arms. However, incidences of gastrointestinal (GI)-related AEs (diarrhea, nausea or vomiting) were lowest, with no grade 3/4 GI AEs reported, in the 450 mg fed arm. Steady-state PK was comparable in advanced ALK+ NSCLC patients taking ceritinib 450 mg with a low-fat meal versus 750 mg fasted. This study continues to enroll treatment-naïve patients into Part 2 to assess efficacy across the three treatment arms and assess longer safety follow-up.