Tedizolid Research Articles

Tedizolid: a novel oxazolidinone with potent activity against multidrug-resistant gram-positive pathogens.

Tedizolid phosphate is a novel oxazolidinone prodrug (converted to the active form tedizolid by phosphatases in vivo) that has been developed and recently approved (June 2014) by the United States FDA for the treatment of acute bacterial skin and skin structure infections (ABSSSIs) caused by susceptible Gram-positive pathogens, including methicillin-resistant Staphylococcus aureus (MRSA). Tedizolid is an oxazolidinone, but differs from other oxazolidinones by possessing a modified side chain at the C-5 position of the oxazolidinone nucleus which confers activity against certain linezolid-resistant pathogens and has an optimized C- and D-ring system that improves potency through additional binding site interactions. The mechanism of action of tedizolid is similar to other oxazolidinones and occurs through inhibition of bacterial protein synthesis by binding to 23S ribosomal RNA (rRNA) of the 50S subunit of the ribosome. As with other oxazolidinones, the spontaneous frequency of resistance development to tedizolid is low. Tedizolid is four- to eightfold more potent in vivo than linezolid against all species of staphylococci, enterococci, and streptococci, including drug-resistant phenotypes such as MRSA and vancomycin-resistant enterococci (VRE) and linezolid-resistant phenotypes. Importantly, tedizolid demonstrates activity against linezolid-resistant bacterial strains harboring the horizontally transmissible cfr gene, in the absence of certain ribosomal mutations conferring reduced oxazolidinone susceptibility. With its half-life of approximately 12 h, tedizolid is dosed once daily. It demonstrates linear pharmacokinetics, has a high oral bioavailability of approximately 90 %, and is primarily excreted by the liver as an inactive, non-circulating sulphate conjugate. Tedizolid does not require dosage adjustment in patients with any degree of renal dysfunction or hepatic dysfunction. Studies in animals have demonstrated that the pharmacodynamic parameter most closely associated with the efficacy of tedizolid is fAUC(0-24h)/MIC. In non-neutropenic animals, a dose-response enhancement was observed with tedizolid and lower exposures were required compared to neutropenic cohorts. Two Phase III clinical trials have demonstrated non-inferiority of a once-daily tedizolid 200 mg dose for 6-10 days versus twice-daily 600 mg linezolid for the treatment of ABSSSIs. Both trials used the primary endpoint of early clinical response at 48-72 h; however, one trial compared oral formulations while the other initiated therapy with the parenteral formulation and allowed oral sequential therapy following initial clinical response. Throughout its development, tedizolid has demonstrated that it is well tolerated and animal studies have shown a lower propensity for neuropathies with long-term use than its predecessor linezolid. Data from the two completed Phase III clinical trials demonstrated that the studied tedizolid regimen (200 mg once daily for 6 days) had significantly less impact on hematologic parameters as well as significantly less gastrointestinal treatment-emergent adverse effects (TEAEs) than its comparator linezolid. As with linezolid, tedizolid is a weak, reversible MAO inhibitor; however, a murine head twitch model validated to assess serotonergic activity reported no increase in the number of head twitches with tedizolid even at doses that exceeded the C max in humans by up to 25-fold. Tyramine and pseudoephedrine challenge studies in humans have also reported no meaningful MAO-related interactions with tedizolid. With its enhanced in vitro activity against a broad-spectrum of Gram-positive aerobic bacteria, convenient once-daily dosing, a short 6-day course of therapy, availability of both oral and intravenous routes of administration, and an adverse effect profile that appears to be more favorable than linezolid, tedizolid is an attractive agent for use in both the hospital and community settings. Tedizolid is currently undergoing additional Phase III clinical trials for the treatment of hospital-acquired bacterial pneumonia (HABP) and ventilated nosocomial pneumonia (VNP).

Stability of crushed tedizolid phosphate tablets for nasogastric tube administration

Tedizolid phosphate, a novel oxazolidinone antibacterial prodrug recently approved by the US Food and Drug Administration for the treatment of acute bacterial skin and skin structure infections, is available as oral (that is, tablets) and intravenous formulations. The clinical pharmacokinetics of tedizolid, the active moiety of tedizolid phosphate, are similar when orally administered tedizolid phosphate is given as powder in a capsule or as tablets. This suggests that crushing tablets prior to administration is unlikely to alter tedizolid pharmacokinetics, provided no drug is lost during administration. To determine whether the expected dose of tedizolid phosphate can be delivered via nasogastric (NG) tube in critically ill patients who have difficulty swallowing, this study evaluated the stability and recovery of tedizolid phosphate 200 mg tablets after crushing, dispersion in water, and passage through an NG tube.

Lack of neuropathological changes in rats administered tedizolid phosphate for nine months.

Tedizolid, a novel oxazolidinone antibacterial, was administered to Long Evans rats by oral gavage once daily for up to 9 months at doses near the maximum tolerated dose (MTD) to evaluate for potential neurotoxicity. Mean plasma exposures of tedizolid at the low-, medium-, and high-dose levels (7.5, 15, and 30 mg/kg of body weight/day for males; 2.5, 5, and 10 mg/kg/day for females) were similar between males and females and were 1.8-, 3.9-, and 8.0-fold greater than exposures in patients at the therapeutic dose (200 mg once daily). Evaluated endpoints included survival, clinical observations, body weight, and food consumption. At 1, 3, 6, and 9 months, ophthalmic examinations, functional observational batteries, and locomotor activity measures were conducted, brain weights/sizes were recorded, and perfusion-fixed tissues were collected from 12 rats/sex/group/time point. A detailed morphological assessment was conducted on brain, eyes, optic nerve/tract, spinal cord, peripheral nerves (includes sciatic, sural, tibial, peroneal, trigeminal), and skeletal muscle. At the end of 9 months, less body weight gain was seen in high-dose males (-6.7%) and females (-5.8%) compared with that seen in controls. There were no tedizolid-related adverse neurobehavioral effects or tedizolid-related histopathologic changes in the central/peripheral nervous systems, including the optic nerve. Results of this study indicate that tedizolid was not neurotoxic when administered long term to pigmented rats at doses near the MTD, which were up to 8-fold higher than the human therapeutic exposure.

Dalbavancin, tedizolid phosphate, oritavancin diphosphate, and vedolizumab

Antibacterial agents Skin and skin structure infections are most often caused by Grampositive bacteria such as streptococci and staphylococci. The number of these infections that are caused by methicillin-resistant Staphylococcus aureus (MRSA) has rapidly increased in recent years in both the community and hospital settings. MRSA skin infections experienced in the community can usually be effectively treated with the oral use of trimethoprim-sulfamethoxazole, clindamycin, or doxycycline. Hospitalized patients with skin and skin structure infections (e.g., cellulitis, major abscess, wound infection) caused by MRSA usually require, at least initially, intravenous treatment with an antibiotic. Vancomycin continues to be highly effective for the treatment of most patients with these infections, but a number of options are available including linezolid (Zyvox), daptomycin (Cubicin), telavancin (Vibativ), and ceftaroline (Teflaro). Linezolid is available in formulations that may be administered intravenously or orally. In 2014, three new antibiotics— dalbavancin (Dalvance—Durata), tedizolid phosphate (Sivextro— Cubist), and oritavancin diphosphate (Orbactiv—The Medicines Company)—have been approved for the treatment of acute bacterial skin and skin structure infections (ABSSSI) caused by susceptible microorganisms. Based on the provisions of the Generating Antibiotic Incentives Now (GAIN) title of the Food and Drug Administration (FDA) Safety and Innovation Act, each of these antibiotics has been designated as a Qualified Infectious Disease Product (QIDP) because it is intended to treat a serious or life-threatening infection. Drugs receiving the QIDP designation are provided an expedited review of their application and qualify for an additional 5 years of marketing exclusivity. Dalbavancin, tedizolid, and oritavancin are considered on an individual basis in the following discussions. Dalbavancin (Dalvance—Durata) is a lipoglycopeptide that is a mixture of five closely related active homologs. It interferes with bacterial cell wall synthesis and exhibits a bactericidal action; and its properties are most similar to those of telavancin. Dalbavancin is administered by intravenous infusion and is specifically indicated for the treatment of adult patients with ABSSSI caused by susceptible isolates of the Gram-positive microorganisms Staphylococcus aureus (S. aureus) (including methicillin-susceptible and methicillin-resistant strains), Streptococcus pyogenes (S. pyogenes), Streptococcus agalactiae (S. agalactiae), and Streptococcus anginosus (S. anginosus) group (including S. anginosus, S. intermedius, and S. constellatus). It should only be used to treat infections that are proven or strongly suspected to be caused by susceptible bacteria. The results of in vitro studies suggest that dalbavancin is also active against vancomycin-susceptible Enterococcus faecium and Enterococcus faecalis (E. faecalis), as well as vancomycin-intermediate S. aureus. Dalbavancin, tedizolid phosphate, oritavancin diphosphate, and vedolizumab

Tedizolid phosphate: Oral and I.V. antibiotic for acute skin infections

Tedizolid phosphate (Sivextro—Cubist Pharmaceuticals), the second antibiotic designated as a qualified infectious disease product (QIDP) for the treatment of acute bacterial skin and skin structure infections (ABSSSI), has received FDA approval. In May, FDA approved dalbavancin (Dalvance—Durata Therapeutics) as a QIDP-designated antibiotic for ABSSSI (see page 31 in the July Pharmacy Today ).

Apremilast.

Each month, subscribers to The Formulary Monograph Service receive 5 to 6 well-documented monographs on drugs that are newly released or are in late phase 3 trials. The monographs are targeted to Pharmacy & Therapeutics Committees. Subscribers also receive monthly 1-page summary monographs on agents that are useful for agendas and pharmacy/nursing in-services. A comprehensive target drug utilization evaluation/medication use evaluation (DUE/MUE) is also provided each month. With a subscription, the monographs are sent in print and are also available on-line. Monographs can be customized to meet the needs of a facility. A drug class review is now published monthly with The Formulary Monograph Service. Through the cooperation of The Formulary, Hospital Pharmacy publishes selected reviews in this column. For more information about The Formulary Monograph Service, call The Formulary at 800-322-4349. The September 2014 monograph topics are tedizolid phosphate, ceritinib, omega-3-carboxylic acids, umeclidinium bromide inhalation powder, and siltuximab. The DUE/MUE is on avoidance of insulin use errors.

Single- and multiple-dose pharmacokinetics and absolute bioavailability of tedizolid.

ObjectivesTedizolid phosphate is a novel antibacterial under investigation for the treatment of gram-positive infections. This study was conducted to assess the pharmacokinetics, safety, and tolerability of intravenous tedizolid phosphate as well as the oral bioavailability of tedizolid phosphate.DesignDouble-blind, single-ascending dose, multiple-dose pharmacokinetics study, as well as tolerability and open-label crossover studies.SettingSingle center in the United States (Covance Clinical Research Unit, Madison, WI) between September 2009 and January 2010.ParticipantsNinety healthy volunteers.InterventionSingle intravenous (IV) doses of tedizolid phosphate 50 mg (lead-in) and 100–400 mg. Single oral and IV dose of tedizolid phosphate 200 mg in crossover fashion. Multiple IV doses of tedizolid phosphate 200 and 300 mg for up to 7 days.Measurements and Main ResultsA dose-dependent increase was observed in the maximum plasma concentration (1.2–5.1 μg/ml) and the area under the concentration-time curve (17.4–58.7 μg × hr/ml) of tedizolid (the microbiologically active moiety of tedizolid phosphate) after single IV doses of tedizolid phosphate 100–400 mg. Administration of IV tedizolid phosphate 200 mg once/day for 7 days resulted in minimal (28%) tedizolid accumulation. The absolute oral bioavailability of tedizolid after a single 200-mg dose of tedizolid phosphate was 91%; pharmacokinetic parameters of tedizolid were similar with oral and IV administration. Treatment-related adverse events occurred in 41% of subjects. Most adverse events were related to infusion site and became more frequent with multiple dosing. In an additional 3-day tolerability study, IV tedizolid phosphate 200 mg and placebo were similarly tolerated, based on visual infusion phlebitis scores.ConclusionThese results from a population of healthy volunteers support once/day dosing of tedizolid phosphate 200 mg with both the oral and IV formulations, without the need for dose adjustment when switching administration routes.

FDA Approves Tedizolid for Skin Infections

On June 20, 2014, the FDA announced approval of tedizolid (Sivextro) for treatment of acute bacterial skin and skin-structure infections (ABSSIs)

Dalbavancin: First I.V. antibiotic for acute bacterial skin infections

Dalbavancin: First I.V. antibiotic for acute bacterial skin infections

Tedizolid phosphate for the treatment of acute bacterial skin and skin structure infections.

Acute bacterial skin and skin structure infections (ABSSSI) are associated with remarkable morbidity, and often require hospitalization. The cause of most ABSSSI is aerobic Gram-positive cocci, including Staphylococcus aureus, and β-hemolytic streptococci. Tedizolid phosphate is a novel oxazolidinone prodrug whose active moiety is tedizolid. It has shown potent in vitro activity against Gram-positive pathogens, encompassing methicillin-resistant S. aureus (MRSA) and strains resistant to vancomycin or linezolid. Animal studies suggested bactericidal activity in vivo. Pharmacokinetic studies demonstrated a good penetration into skin and soft tissues, and suitability for once-daily administration, either orally or intravenously at the same dosage. Pivotal phase III studies showed that tedizolid phosphate at 200 mg once daily for 6 days is noninferior to linezolid 600 mg twice daily for 10 days in ABSSSI patients, whereas gastrointestinal disorders were less frequent with tedizolid phosphate than linezolid. Tedizolid phosphate has been approved by the U.S. FDA, as Sivextro® to treat adult patients with ABSSSI.

Tedizolid: A Novel Oxazolidinone for Gram-Positive Infections

Tedizolid: A Novel Oxazolidinone for Gram-Positive Infections

Use of Pharmacokinetic/Pharmacodynamic Systems Analyses to Inform Dose Selection of Tedizolid Phosphate

In the Staphylococcus aureus neutropenic murine thigh-infection model, the ratio of the free area under the 24-hour concentration-time curve to the minimum inhibitory concentration (fAUC/MIC) was found to be the pharmacodynamic index most closely linked to bacterial effect, with a ratio of approximately 50 producing a static effect. Further work was undertaken in neutropenic versus non-neutropenic animals. The presence of granulocytes increased the activity of tedizolid considerably, 25-fold on average, and maximal effect was achieved at an exposure equivalent to approximately 200 mg tedizolid phosphate per day in humans (dosing regimen used in phase 2 and 3 clinical trials). The fAUC/MIC was also found to be the pharmacodynamically linked variable in the S. aureus neutropenic murine pneumonia model; the fAUC/MIC ratio required for a static effect was approximately 20. Pharmacokinetic (PK) data demonstrate that tedizolid penetrates well into the epithelial lining fluid (ELF) of the lung. Data from the pneumonia infection model and ELF penetration PK study support exploring its use in pneumonia.

Intracellular activity of tedizolid phosphate and ACH-702 versus Mycobacterium tuberculosis infected macrophages

BackgroundDue to the emergency of multidrug-resistant strains of Mycobacterium tuberculosis, is necessary the evaluation of new compounds.FindingsTedizolid, a novel oxazolidinone, and ACH-702, a new isothiazoloquinolone, were tested against M. tuberculosis infected THP-1 macrophages. These two compounds significantly decreased the number of intracellular mycobacteria at 0.25X, 1X, 4X and 16X the MIC value. The drugs were tested either in nanoparticules or in free solution.ConclusionTedizolid and ACH-702 have a good intracellular killing activity comparable to that of rifampin or moxifloxacin.

Tedizolid Phosphate for the Management of Acute Bacterial Skin and Skin Structure Infections: Efficacy Summary

The novel oxazolidinone tedizolid phosphate is in late-stage development for acute bacterial skin and skin structure infections (ABSSSIs). Preclinical and phase 1 trials have shown that 200-mg once-daily tedizolid phosphate dosing achieves the appropriate pharmacokinetic goals for optimal antimicrobial effect, and a randomized phase 2 dose-ranging trial confirmed that tedizolid phosphate may be an option for the treatment of ABSSSIs at the 200-mg dose, the lowest effective dose, over a mean of 6.4 days of therapy. In the first of two phase 3 trials, 6 days of 200-mg once-daily oral tedizolid phosphate (plus 4 days of placebo) was noninferior to 10 days of 600-mg twice-daily oral linezolid when evaluated at both the early (48- to 72-hour assessment) and test-of-cure (7-14 days after the last dose of active or placebo agent was given) time points. Initial results from the second phase 3 trial (intravenous to oral therapy design) confirm the study met all primary and secondary endpoints and continues to add insight into the clinical utility of tedizolid phosphate.

Tedizolid Phosphate for the Management of Acute Bacterial Skin and Skin Structure Infections: Safety Summary

The novel oxazolidinone tedizolid phosphate is in late-stage clinical development. In an effort to improve efficacy and safety, the adverse event profile and safety aspects of tedizolid phosphate have been evaluated in several preclinical animal models and through ongoing clinical trials. Early dose-ranging studies demonstrated a favorable overall adverse event profile and low thrombocytopenia rates, which have been consistently confirmed in phase 2 and 3 clinical trials. Pharmacokinetic modeling suggests a lower potential for monoamine oxidase interaction, and animal and human subject testing has confirmed these predictions. Studies in special patient populations showed a consistent and predictable pharmacokinetic profile across age groups and comorbid conditions, without evidence of increased incidence of adverse effects over matched controls. The favorable safety profile makes tedizolid phosphate an important new option for the management of serious Gram-positive infections, including those caused by methicillin-resistant Staphylococcus aureus.

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Introduction: Tedizolid phosphate (TZP) is in Phase III clinical development globally for infections caused by Gram-positive bacteria, including MRSA. The pharmacokinetic (PK) properties of the active moiety tedizolid after intravenous (IV) and oral (PO) administration of TZP had previously been evaluated in healthy American subjects. This Phase I study assessed the PK profile of tedizolid in healthy Japanese adults prior to its Phase III investigation for nosocomial pneumonia. Methods: In this two-way crossover study, subjects were randomized to receive IV placebo (saline, n=4) or 200 mg TZP (n=8) in 250 ml infusion over 60 minutes. After a 7-day washout period, subjects randomly received an oral dose of either placebo (n=4) or 200 mg TZP (n=8) with 240 mL water. Plasma samples were collected at baseline and at subsequent time points up to 72 hours after administration. The concentration of tedizolid was determined by LC-MS/MS assay and PK parameters were calculated. Data are expressed as (arithmetic) mean ± standard deviation. Results: Due to a mild adverse event, TZP infusion was discontinued in one subject, who was then excluded from the entire PK analysis. After IV administration of TZP, the plasma concentration of tedizolid reached a Cmax of 3.45 ± 0.60 μg/mL within ~1 hour (Tmax=1.08h) and decreased with a half-life (t1/2) of 10.8 ± 1.37 hours. The total drug exposure (AUC) was 34.4 ± 7.9 μg•h/mL. After PO administration of TZP, the tedizolid plasma concentration reached a Cmax of 2.38 ± 0.59 μg/mL within ~3 hours, then it decreased with a t1/2 of 10.7 ± 0.99 hours; the AUC was 28.6 ± 8.2 μg•h/mL. Conclusions: The PK profile of the active moiety tedizolid was similar after IV and PO administration of TZP in healthy Japanese adults and was comparable to the profile previously observed in American subjects in a similar study (IV: Cmax=2.48 ± 0.41 μg/mL, t1/2=11.4 ± 2.00 h, AUC=29.0 ± 6.14 μg•h/mL; PO: Cmax=1.91 ± 0.44 μg/mL, t1/2=11.1 ± 2.12 h, AUC=26.7 ± 6.0 μg•h/mL), with slightly higher exposures (Cmax, AUC) even after correcting for body weight. In summary, no major differences in the PK profile of tedizolid were observed due to subject ethnicity and no TZP dose adjustment is recommended for Japanese adults.

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Introduction: Some antibiotics used for treating ventilator-associated bacterial pneumonia (VABP) are associated with mitochondrial toxicity that can manifest as serious optic and/or peripheral neuropathy. Tedizolid phosphate (TZP), a novel antibiotic prodrug currently in clinical development for VABP, may have reduced potential for mitochondrial toxicity. This study was conducted to evaluate the potential for drug-induced optic and peripheral neuropathies with TZP at the 200 mg once daily dose used in the VABP Phase 3 program. Methods: This was a Phase 1 open-label study in healthy male and female volunteers (18-65 years old) who received oral TZP 200 mg once daily for 10 days and underwent extensive ophthalmologic and neurologic assessments before and after study drug administration and 2 - 4 weeks after the last dose. Ophthalmologic assessments included optical coherence tomography, best corrected distance visual acuity, dilated fundoscopy, color vision testing (Roth 28), dilated and non-dilated slit lamp examination, visual field testing (Haag-Streit Octopus 300), and optic nerve photography. Neurologic assessments included cranial nerve, sensory, motor, reflex, coordination, and gait evaluations. Results: A total of 72 subjects were enrolled; 67 completed the study (i.e., received all 10 doses of study drug and underwent all study visits). Five subjects withdrew from the study for personal reasons. There were no discontinuations or withdrawals due to treatment emergent adverse events (TEAEs). All subjects had normal neurologic assessments at all study time points. Minor changes in ophthalmologic examinations were observed, but none were deemed clinically meaningful. TEAEs were reported in approximately 30% of subjects. The most common TEAEs were headache, musculoskeletal pain, nausea, diarrhea, and nasal congestion. All TEAEs were mild in severity; there were no serious AEs or deaths. Conclusions: There was no evidence of neurologic and ophthalmologic changes suggestive of peripheral or optic neuropathy in healthy volunteers who received oral TZP 200 mg once daily for 10 days. These results add to the cumulative evidence supporting the ongoing clinical development of TZP for critically ill patients.

Pharmacokinetics of Tedizolid Following Oral Administration: Single and Multiple Dose, Effect of Food, and Comparison of Two Solid Forms of the Prodrug

ObjectivesThe single- and multiple-dose pharmacokinetics (PK) of tedizolid were examined after oral administration of tedizolid phosphate disodium (TPD), including the effect of food on PK. The relative bioavailability of TPD to the free acid tedizolid phosphate was determined to bridge the results of these and other studies to the solid form of the prodrug selected for further development.DesignRandomized placebo-controlled, double-blind single- and multiple-ascending dose studies and randomized open-label, crossover food effect and relative bioavailability studies.SettingClinical Research Units.ParticipantsHealthy subjects.InterventionStudy TR701-101 enrolled 40 subjects in single-ascending dose (200–1200 mg TPD or placebo) and 40 subjects in 21-day multiple-ascending dose (200, 300, or 400 mg TPD once/day; 600 mg linezolid twice/day; or placebo) arms. Study TR701-103 was a food-effect study in 12 subjects administered 600 mg TPD. Study TR701-108 was a relative bioavailability study in 12 subjects administered 150-mg tedizolid equivalents as TPD or tedizolid phosphate.Measurements and Main ResultsPlasma concentrations of the prodrug tedizolid phosphate, its active moiety tedizolid, and/or linezolid were collected. After administration of 200 to 600 mg TPD, tedizolid values increased approximately dose proportionally in area under the concentration-time curve (AUC) and maximum plasma concentration (Cmax). Tedizolid half-life values were approximately 2-fold greater compared with linezolid. TPD administration with food delayed tedizolid absorption and reduced Cmax relative to the fasted state but did not alter AUC. Minimal accumulation was predicted and observed for tedizolid, whereas observed accumulation of linezolid exceeded predictions based on single-dose PK. Comparable PK of tedizolid was observed following oral administration of either TPD or tedizolid phosphate. In the multiple-ascending dose study, 3 of 24 tedizolid subjects were withdrawn under prespecified stopping rules (one each of elevated alanine aminotransferase, low reticulocyte count, or low white blood cell count), as was 1 of 8 linezolid subjects (low reticulocyte count).ConclusionsOverall, tedizolid has a favorable PK profile, a half-life that supports once daily administration, and no nonlinearities at steady state. Tedizolid phosphate can be administered without regard to food.

Alogliptin

Each month, subscribers to The Formulary Monograph Service receive 5 to 6 well-documented monographs on drugs that are newly released or are in late phase 3 trials. The monographs are targeted to Pharmacy & Therapeutics Committees. Subscribers also receive monthly 1-page summary monographs on agents that are useful for agendas and pharmacy/nursing in-services. A comprehensive target drug utilization evaluation/medication use evaluation (DUE/MUE) is also provided each month. With a subscription, the monographs are sent in print and are also available on-line. Monographs can be customized to meet the needs of a facility. A drug class review is now published monthly with The Formulary Monograph Service. Through the cooperation of The Formulary, Hospital Pharmacy publishes selected reviews in this column. For more information about The Formulary Monograph Service, call The Formulary at 800-322-4349. The July 2013 monograph topics are prothrombin complex concentrate (human), cysteamine bitartrate delayed-release capsules, doxylamine succinate/pyridoxine hydrochloride, tedizolid phosphate, and sofosbuvir. The DUE/MUE is on canaglifozin.

A phase 1 study of intravenously administered TR-701 FA in subjects with advanced renal impairment

The objective of the study was to characterize the safety of tedizolid phosphate (TR-701 FA) and the pharmacokinetics of tedizolid (TR-700), its microbiologically active moiety, in subjects with advanced renal impairment (eGFR <30 ml/minute/1.73 m2, not on dialysis) compared with matched subjects with normal renal function (eGFR ≥80.0 ml/minute/1.73 m2).