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

NCT ID: NCT04309656

Last Updated: 2024-07-24

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 48 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-01-14
• Study Completion Date: 2020-02-28

Brief Summary

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

Detailed 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.

Conditions

Multi-drug Resistant Tuberculosis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Panel 1: Pretomanid after meal

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.

Group Type: EXPERIMENTAL

Pretomanid

Intervention Type: DRUG

1. Treatment A (reference) = 200 mg given as a single 200 mg tablet (using the immediate release formulation), orally administered.

2. Treatment B (test) = 200 mg given as four 50-mg tablets (using the dispersible pediatric formulation), orally administered.

3. Treatment C (test) = single 50-mg dispersible tablet, orally administered.

4. Treatment D (test) = single 10-mg dispersible tablet, orally administered.

Panel 2: Pretomanid after fast

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

Group Type: EXPERIMENTAL

Pretomanid

Intervention Type: DRUG

1. Treatment A (reference) = 200 mg given as a single 200 mg tablet (using the immediate release formulation), orally administered.

2. Treatment B (test) = 200 mg given as four 50-mg tablets (using the dispersible pediatric formulation), orally administered.

3. Treatment C (test) = single 50-mg dispersible tablet, orally administered.

4. Treatment D (test) = single 10-mg dispersible tablet, orally administered.

Interventions

Pretomanid

1. Treatment A (reference) = 200 mg given as a single 200 mg tablet (using the immediate release formulation), orally administered.

2. Treatment B (test) = 200 mg given as four 50-mg tablets (using the dispersible pediatric formulation), orally administered.

3. Treatment C (test) = single 50-mg dispersible tablet, orally administered.

4. Treatment D (test) = single 10-mg dispersible tablet, orally administered.

Intervention Type: DRUG

Other Intervention Names

PA-824

Eligibility Criteria

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.

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).

• Minimum Eligible Age: 19 Years
• Maximum Eligible Age: 50 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Global Alliance for TB Drug Development

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Antonio Lombardi, MD

Role: STUDY_DIRECTOR

TB Alliance

Locations

Worldwide Clinical Trials Early Phase Services, LLC

San Antonio, Texas, United States

Countries

United States

References

Zou Y, Nedelman J, Lombardi A, Pappas F, Karlsson MO, Svensson EM. Characterizing Absorption Properties of Dispersible Pretomanid Tablets Using Population Pharmacokinetic Modelling. Clin Pharmacokinet. 2022 Nov;61(11):1585-1593. doi: 10.1007/s40262-022-01163-w. Epub 2022 Sep 30.

Reference Type: DERIVED

PMID: 36180816 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

Pa-824-CL-011

Identifier Type: -

Identifier Source: org_study_id