A Study in Two Panels of Healthy Adult Participants to Assess Single-Dose Immediate-Release and Single-Dose Dispersible Formulations of Pretomanid

• Status: Completed
• Trial end date: 2020-02-28
• Target enrollment: 0
• Participant gender: All

Summary

This is a single-dose, open-label, randomized, four-period, four-treatment, crossover study in healthy adult subjects.

• Phase: Phase 1
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: Global Alliance for TB Drug Development

Criteria

Inclusion Criteria:

• Voluntarily consents to participate in this study and provides written informed consent before the start of any study-specific procedures.

• Male or female. Females must not be pregnant or breastfeeding.

• Willing and able to comply with the contraception requirements.

• Between 19 and 50 years of age (inclusive) at the time of screening.

• Body mass index (BMI) between 18.50 and 32 kg/m2 (inclusive) and weighs a minimum of 50 kg.

• Willing and able to remain in the study unit for the entire confinement period and return for the outpatient follow-up visit.

• Willing and able to consume the entire high-calorie, high-fat breakfast meal in the timeframe required during the designated study period.

• Willing and able to comply with the protocol and the assessments therein, including all restrictions.

Exclusion Criteria:

• History or presence of clinically significant cardiovascular, pulmonary, hepatic, renal, hematologic, gastrointestinal, endocrine, immunologic, dermatologic, neurologic, oncologic, or psychiatric disease or any other condition that, in the opinion of the Investigator, would jeopardize the safety of the subject or the validity of the study results.

• A clinically significant abnormal finding on the physical examination, medical history, electrocardiogram (ECG), or clinical laboratory results.

• Vital signs at screening (measured sitting after a minimum 3 minutes rest) as follows:

blood pressure is less than 90/40 mmHg or greater than 140/90 mmHg or a heart rate lower than 40 bpm or higher than 99 bpm. Out-of-range vital signs may be repeated once.

• History or presence of allergic or adverse response to pretomanid or related drugs.

• On a significantly abnormal diet during the 4 weeks preceding the first dose of study medication.

• Participation in another clinical trial (randomized subjects only) within 30 days before the first dose of study medication.

• Use of any over-the-counter (OTC) medication (including nutritional or dietary supplements, herbal preparations, or vitamins) within 7 days before the first dose of study medication until the end of study visit without evaluation and approval by the Investigator. Up to 3 grams per day of acetaminophen is allowed at the discretion of the Investigator prior to dosing.

• Use of any prescription medication, except hormonal contraceptive or hormonal replacement therapy, from 14 days before the first dose of study medication until the end-of-study visit without evaluation and approval by the Investigator.

• Use of any drugs or substances known to lower the seizure threshold.

• Use of any drugs or treatment with any known drugs that are moderate or strong inducers or inhibitors of cytochrome P450 (CYP) enzymes (e.g., barbiturates, phenothiazines, cimetidine, carbamazepine) and/or P-gp, including St. John's Wort, within 30 days before the first dose of study medication, and that, in the Investigator's judgment, may impact subject safety or the validity of the study results.

• Female with a positive pregnancy test result.

• Positive urine screen for drugs of abuse (amphetamines, barbiturates, benzodiazepines, cocaine, cannabinoids, opiates) or cotinine.

• Positive test for hepatitis B surface antigen, hepatitis C antibody, or human immunodeficiency virus (HIV) at screening or has been previously treated for hepatitis B, hepatitis C, or HIV infection.

• Hemoglobin <10.0 g/dL.

• ALT (alanine transaminase) or AST (aspartate aminotransferase) >2.0 x the upper limit of normal (ULN).

• Hyperbilirubinemia >1.5 x ULN.

• Surgery within the past 90 days prior to dosing as determined by the Investigator to be clinically relevant.

• History or presence of alcoholism or drug abuse within the past 2 years as determined by the Investigator to be clinically relevant.

• Any clinically significant electrocardiogram abnormality at Screening (as deemed by decision of the Investigator and the Study Sponsor's Medical Monitor).

• QTcF interval >450 msec for males or >470 msec for females at screening, Day -1, or Day 1 (pre-dose), or history of prolonged QT syndrome.

• Family history of Long-QT Syndrome or sudden death without a preceding diagnosis of a condition that could be causative of sudden death (such as known coronary artery disease, congestive heart failure or terminal cancer).