A Study of the Safety, Tolerability, and Absorption, Metabolism, and Excretion of PA-824 in Healthy Adult Male Subjects.

NCT03202693 | Completed Phase 1

• 1 other identifier: PA 824-CL-004
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 1

Brief Summary

This study is a Phase 1, single-center, open-label, single-dose study to evaluate (1) the absorption, metabolism, and excretion patterns of a single dose of \[14C\] PA-824, and (2) the pharmacokinetics, safety, and tolerability of a single oral-suspension dose of unlabeled PA-824 in healthy adult male subjects. Unlabeled PA-824 and \[14C\]-PA-824 will be administered together in an oral-suspension formulation. Enrollment is planned for one dose group of 6 subjects. All 6 subjects will receive the same treatment.

Conditions

Tuberculosis

Keywords

Tuberculosis, PA-824

Outcome Measures

Primary Outcomes (3)

• Characterize the plasma pharmacokinetic variable area under the curve of a single oral-suspension dose of PA-824.

  Characterize the plasma pharmacokinetics of a single oral-suspension dose of PA-824 in healthy adult male subjects by calculating the variable area under the curve \[AUC (0-t)\] from total PA-824 plasma concentrations.

  Days 0-12

• Characterize the plasma pharmacokinetic variable maximum concentration of a single oral-suspension dose of PA-824.

  Characterize the plasma pharmacokinetics of a single oral-suspension dose of PA-824 in healthy adult male subjects by calculating the variable maximum plasma concentration (Cmax) from total PA-824 plasma concentrations.

  Days 0-12

• Characterize the plasma pharmacokinetic variable time to peak plasma concentration of a single oral-suspension dose of PA-824.

  Characterize the plasma pharmacokinetics of a single oral-suspension dose of PA-824 in healthy adult male subjects by calculating the variable time to peak plasma concentration (Tmax) from total PA-824 plasma concentrations.

  Days 0-12

Secondary Outcomes (1)

• The frequency and severity of treatment related adverse events throughout the study.

  Days 0 -12

Study Arms (1)

PA-824

EXPERIMENTAL

\[14C\]-PA-824 and unlabelled PA-824 oral suspension of 1000 mg unlabeled micronized PA-824 mixed with sufficient \[14C\]-PA-824 to achieve a final radiolabel dose of approximately 100 µCi/dose.

Drug: PA-824

Interventions

PA-824 DRUG

PA-824

Eligibility Criteria

• Age: 19 Years - 50 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Be healthy non-tobacco/nicotine using (6-month minimum) adult male subjects, 19 to 50 years of age, inclusive
• Weigh within 20% of their ideal weights (Table of "Desirable Weights of Adults", Metropolitan Life Insurance Company, 1999)
• Be medically healthy subjects with clinically insignificant Screening results (among laboratory profiles, medical histories, ECGs, or physical exam), as deemed by the Principal Investigator in consultation with the Sponsor Medical Monitor.
• Have a history of regular bowel movements (5-6 movements week, ideally 1 per day), as deemed by the Principal Investigator in consultation with the Sponsor Medical Monitor.
• Have negative urinalysis test results for drugs of abuse such as amphetamines, cannabinoids, and cocaine metabolites
• Have the ability to understand the requirements of the study, have provided written informed consent (as evidenced by signature on an informed consent document approved by an IRB), and agree to abide by the study restrictions

You may not qualify if:

• Any acute illness or history or presence of significant (as deemed by the Principal Investigator) cardiovascular, pulmonary, hepatic, renal, hematologic, gastrointestinal, endocrine, immunologic, dermatologic, neurologic, or psychiatric disease
• Any preexisting condition that would interfere with normal anatomy or function of the gastrointestinal tract.
• Any medical condition that would interfere with radiocarbon assessments.
• Any serum creatinine or BUN measure beyond the upper limit of the normal range at Screening or Check-in.
• Positive Screening test for HCV, HBV, or HIV
• History of peptic ulcer disease, gastritis, esophagitis, or gastroesophageal reflux disease
• History of any cardiac abnormality (as deemed by the Principal Investigator)
• History of hypokalemia or hypomagnesemia
• History of prolonged QT interval
• Family history of Long-QT Syndrome or sudden death
• Resting pulse rate \< 40 or \> 100 bpm at both Screening and Check-in
• QTc interval \> 430 msec as documented at Screening and Baseline (Check-in) ECG
• History or presence of alcoholism or drug abuse within the past year (as deemed by the Principal Investigator)
• Use of alcohol within 72 hours prior to dosing
• Significant history of drug and/or food allergies (as deemed by the Principal Investigator)

Sponsors & Collaborators

• Global Alliance for TB Drug Development: lead

Study Sites (1)

Covance Clinical Research Unit

Madison, Wisconsin, 53704, United States

Location

MeSH Terms

Conditions

Tuberculosis

Interventions

pretomanid

Condition Hierarchy (Ancestors)

Mycobacterium Infections; Actinomycetales Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections

Study Officials

• William Bridson, MD

  Covance CRU

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 1, 2017
• First Posted: June 28, 2017
• Study Start: March 1, 2006
• Primary Completion: May 1, 2006
• Study Completion: May 1, 2006
• Last Updated: August 2, 2018

Record last verified: 2018-02

Locations

US (1)