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

Global Alliance for TB Drug Development

Status and phase: Completed; Phase 1

Conditions: Multi-drug Resistant Tuberculosis

Treatments: Drug: Pretomanid

Study type: Interventional

Funder types: Other

Identifiers

NCT04309656

Pa-824-CL-011

Details and patient eligibility

About

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

Full description

This is a single-dose, open-label, randomized, four-period, four-treatment, crossover study in healthy adult subjects. Each panel of 24 subjects will be randomized according to the same 4-sequence, 4- period Williams design, in which each participant will receive four single-dose treatments. Subjects in Panel 1 will receive all treatments after consuming an FDA standard high-fat, high-calorie breakfast following an overnight fast of at least 10 hours. Subjects in Panel 2 will receive all treatments directly following an overnight fast of at least 10 hours. The two panels will be investigated concurrently.

Enrollment: 48 patients

Sex: All

Ages: 19 to 50 years old

Volunteers: Accepts Healthy Volunteers

Inclusion and exclusion criteria

Key Inclusion Criteria:

• 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.

Key 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.
• 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.
• 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 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.
• 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).

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: None (Open label)

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48 participants in 2 patient groups

Panel 1: Pretomanid after meal

Experimental group

Description:

Each participant will receive four single-dose treatments with a 7-day washout period between each dose. Panel 1 will receive a meal before dosing.

Treatment:

Drug: Pretomanid

Panel 2: Pretomanid after fast

Experimental group

Description:

Each participant will receive four single-dose treatments with a 7-day washout period between each dose. Panel 2 will fast before dosing.

Treatment:

Drug: Pretomanid