Phase 2
N=26
A Trial to Evaluate the Male Reproductive Safety of Pretomanid in Adult Male Participants With Drug Resistant Pulmonary Tuberculosis
Tuberculosis, Pulmonary · Tuberculosis, Multidrug-Resistant · Tuberculosis, MDR · Tuberculosis · Drug-Resistant Tuberculosis
Bottom Line
View on ClinicalTrials.gov: NCT04179500 ↗Enrolled (actual)
26
Serious AEs
7.7%
Results posted
Sep 2024
Primary outcome: Primary: Change Form Baseline Total Sperm Count — 20 10^6 sperm cells/ejaculate
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- Pretomanid (Drug); Bedaquiline (Drug); moxifloxacin (Drug); pyrazinamide (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- Male
- Sponsor
- Global Alliance for TB Drug Development
- Primary completion
- Jun 2023
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Change Form Baseline Total Sperm Count |
20 | — |
| SECONDARY Change From Baseline in Total Sperm Count at 12 Weeks |
4.2 | — |
| SECONDARY Change From Baseline Total Sperm Count at 44 Weeks |
4.4 | — |
| SECONDARY Luteinizing Hormone (LH) |
5.8; 4.6; 3.6; 4.0 | — |
| SECONDARY FSH |
6.6; 6.2; 5.2; 4.6 | — |
| SECONDARY Testosterone |
547; 600; 646; 615.5 | — |
| SECONDARY Inhibin B |
122; 137; 162.5; 172 | — |
Summary
Pretomanid is being used in an antimicrobial combination regimen(s) to treat patients with pulmonary tuberculosis (TB). The primary purpose of the Male Reproductive Safety - "BPaMZ/SEM"- clinical study is to evaluate the potential effect of pretomanid on human testicular function whilst being used in a 26 weeks antimicrobial combination regimen consisting of bedaquiline (B) plus pretomanid (Pa) plus moxifloxacin (M) and pyrazinamide (Z) (BPaMZ).
Eligibility Criteria
Inclusion Criteria
- Understands study procedures and voluntarily provides written informed consent prior to the start of any study-specific procedures.
- Male gender 18 years or over
- Body weight (in light clothing and no shoes) ≥ 45kg.
- A positive molecular test for tuberculosis in sputum either at screening or within one month prior to enrolment.
- Disease Characteristics:
- Participants must have been diagnosed with TB prior to or at screening
- Participants' TB should be resistant to rifampicin and/or isoniazid, and susceptible to fluoroquinolones by rapid sputum-based tests.
- Participants who have had previous treatment for DR-TB for more than 3 months at start of screening should be discussed with the medical monitor.
- A chest x-ray, within 26 weeks prior to or at the screening visit, which in the opinion of the Investigator is compatible with pulmonary TB
Exclusion criteria
- Resistant to fluoroquinolones by rapid molecular test
- History of male infertility or vasectomy
- Unable to produce semen sample
- Evidence at screening of azoospermia
- Known erectile dysfunction that would prevent ejaculation.
- Historical or active disease process of the male reproductive tract that would compromise sperm production. e.g. tuberculous epididymitis.
- History of any illness that, in the opinion of the Investigator, might confound the results of the study or poses an additional risk to the participant by their participation in the study.
- For HIV infected participants any of the following:
- CD4+ count 1.5 times upper limit of normal (ULN)
- eGFR ≤ 60 mL/min
- Haemoglobin 1.5 x ULN to be excluded
- Greater than ULN must be discussed with and approved by the Sponsor Medical Monitor
- Direct bilirubin:
- greater than 1x ULN to be excluded
- Positive hepatitis B surface Ag, or hepatitis C antibody
Data sourced from ClinicalTrials.gov (NCT04179500). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.