A Phase 1 Multiple Dose Trial in Healthy Adult Participants to Evaluate the Safety, Tolerability, Drug-Drug Interactions, and Pharmacokinetics of TBD11

NCT07883226 | Not Yet Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: Gates MRI-TBD11-104
• Study Type: interventional
• Target: 66
• Locations: 1 country
• Sites: 1

Brief Summary

This is a Phase 1, randomized, double-blind, placebo-controlled, multiple dose trial of TBD11 in healthy adults. It includes a dedicated open-label cohort in which TBD11 will be administered as a single dose with either a strong cytochrome P450 3A (CYP3A) inhibitor (itraconazole) or a strong CYP3A inducer (rifampicin) in 2 trial periods to evaluate DDI. The trial will consist of 3 cohorts; Cohort 1 will occur prior to Cohort 2 and Cohort 3. Cohort 2 and Cohort 3 will start after completion of Cohort 1 and will run in parallel. Cohort 1 will be double-blind and participants will receive 300 mg TBD11 or placebo once daily for 14 days. Cohort 2 will be the open-label DDI cohort. Cohort 3 will be double-blind and participants will receive TBD11 or placebo once daily for 84 days.

Conditions

Healthy Adult Participants

Keywords

Mycobacterium tuberculosis; TBD11; Rifampicin; Itraconazole; Multiple Dose; Drug-Drug Interactions; Fixed Daily Dosing; Safety; Tolerability; Pharmacokinetics; DDI

Outcome Measures

Primary Outcomes (19)

• Number of Participants With Treatment-Emergent Adverse Events

  Number of participants with one or more treatment-emergent adverse events, summarized overall and by severity, Investigator-assessed relationship to trial intervention, System Organ Class, and Preferred Term.

  Cohort 1: Day 1 through Day 19. Cohort 2 Arm A: Period 1, Day 1 through Day 8; Period 2, Day -4 through Day 16. Cohort 2 Arm B: Period 1, Day 1 through Day 8; Period 2, Day -10 through Day 8. Cohort 3: Day 1 through Day 92.

• Number of Participants With Serious Adverse Events

  Number of participants with one or more serious adverse events, summarized overall and by severity, Investigator-assessed relationship to trial intervention, System Organ Class, and Preferred Term.

  Cohort 1: Day 1 through Day 19. Cohort 2 Arm A: Period 1, Day 1 through Day 8; Period 2, Day -4 through Day 16. Cohort 2 Arm B: Period 1, Day 1 through Day 8; Period 2, Day -10 through Day 8. Cohort 3: Day 1 through Day 92.

• Number of Participants With Adverse Events Leading to Trial Intervention Interruption

  Number of participants with one or more adverse events resulting in temporary interruption of trial intervention, summarized overall and by severity, Investigator-assessed relationship to trial intervention, System Organ Class, and Preferred Term.

  Cohort 1: Day 1 through Day 19. Cohort 2 Arm A: Period 1, Day 1 through Day 8; Period 2, Day -4 through Day 16. Cohort 2 Arm B: Period 1, Day 1 through Day 8; Period 2, Day -10 through Day 8. Cohort 3: Day 1 through Day 92.

• Number of Participants With Adverse Events Leading to Trial Intervention Discontinuation

  Number of participants with one or more adverse events resulting in permanent discontinuation of trial intervention, summarized overall and by severity, Investigator-assessed relationship to trial intervention, System Organ Class, and Preferred Term.

  Cohort 1: Day 1 through Day 19. Cohort 2 Arm A: Period 1, Day 1 through Day 8; Period 2, Day -4 through Day 16. Cohort 2 Arm B: Period 1, Day 1 through Day 8; Period 2, Day -10 through Day 8. Cohort 3: Day 1 through Day 92.

• Number of Participants With Treatment-Emergent Clinical Chemistry Abnormalities

  Number of participants with treatment-emergent clinical chemistry abnormalities, summarized by visit, worst post-baseline grade, and grade shift from baseline using the protocol-specified toxicity grading criteria.

  Cohort 1, Day 1 through Day 19; Cohort 2 Arm A, Period 1 Day 1 through Day 8 and Period 2 Day -4 through Day 16; Cohort 2 Arm B, Period 1 Day 1 through Day 8 and Period 2 Day -10 through Day 8; Cohort 3, Day 1 through Day 92.

• Number of Participants With Treatment-Emergent Hematology Abnormalities

  Number of participants with treatment-emergent hematology abnormalities, summarized by visit, worst post-baseline grade, and grade shift from baseline using the protocol-specified toxicity grading criteria.

  Cohort 1, Day 1 through Day 19; Cohort 2 Arm A, Period 1 Day 1 through Day 8 and Period 2 Day -4 through Day 16; Cohort 2 Arm B, Period 1 Day 1 through Day 8 and Period 2 Day -10 through Day 8; Cohort 3, Day 1 through Day 92.

• Number of Participants With Treatment-Emergent Coagulation Abnormalities

  Number of participants with treatment-emergent coagulation abnormalities, summarized by visit, worst post-baseline grade, and grade shift from baseline using the protocol-specified toxicity grading criteria.

  Cohort 1, Day 1 through Day 19; Cohort 2 Arm A, Period 1 Day 1 through Day 8 and Period 2 Day -4 through Day 16; Cohort 2 Arm B, Period 1 Day 1 through Day 8 and Period 2 Day -10 through Day 8; Cohort 3, Day 1 through Day 92.

• Number of Participants With Treatment-Emergent Urinalysis Abnormalities

  Number of participants with treatment-emergent urinalysis abnormalities, summarized by visit, worst post-baseline grade, and grade shift from baseline using the protocol-specified toxicity grading criteria.

  Cohort 1, Day 1 through Day 19; Cohort 2 Arm A, Period 1 Day 1 through Day 8 and Period 2 Day -4 through Day 16; Cohort 2 Arm B, Period 1 Day 1 through Day 8 and Period 2 Day -10 through Day 8; Cohort 3, Day 1 through Day 92.

• Number of Participants With Treatment-Emergent Lipid Profile Abnormalities

  Number of Cohort 3 participants with treatment-emergent lipid profile abnormalities, summarized by visit, worst post-baseline grade, and grade shift from baseline.

  Baseline and scheduled post-baseline assessments from Day 1 through Day 92 for Cohort 3.

• Change From Baseline in Systolic Blood Pressure

  Change from baseline in systolic blood pressure, measured in millimeters of mercury (mmHg).

  Cohort 1, Day 1 through Day 19; Cohort 2 Arm A, Period 1 Day 1 through Day 8 and Period 2 Day -4 through Day 16; Cohort 2 Arm B, Period 1 Day 1 through Day 8 and Period 2 Day -10 through Day 8; Cohort 3, Day 1 through Day 92.

• Change From Baseline in Diastolic Blood Pressure

  Change from baseline in diastolic blood pressure, measured in millimeters of mercury (mmHg)

  Cohort 1, Day 1 through Day 19; Cohort 2 Arm A, Period 1 Day 1 through Day 8 and Period 2 Day -4 through Day 16; Cohort 2 Arm B, Period 1 Day 1 through Day 8 and Period 2 Day -10 through Day 8; Cohort 3, Day 1 through Day 92.

• Change From Baseline in Heart Rate

  Change from baseline in heart rate, measured in beats per minute (bpm)

  Cohort 1, Day 1 through Day 19; Cohort 2 Arm A, Period 1 Day 1 through Day 8 and Period 2 Day -4 through Day 16; Cohort 2 Arm B, Period 1 Day 1 through Day 8 and Period 2 Day -10 through Day 8; Cohort 3, Day 1 through Day 92.

• Change From Baseline in Body Temperature

  Change from baseline in body temperature, measured in degrees Celsius (°C)

  Cohort 1, Day 1 through Day 19; Cohort 2 Arm A, Period 1 Day 1 through Day 8 and Period 2 Day -4 through Day 16; Cohort 2 Arm B, Period 1 Day 1 through Day 8 and Period 2 Day -10 through Day 8; Cohort 3, Day 1 through Day 92.

• Change From Baseline in 12-Lead ECG Heart Rate

  Change From Baseline in 12-Lead ECG Heart Rate Change from baseline in 12-lead ECG heart rate, measured in beats per minute (bpm)

  Cohort 1, Day 1 through Day 19; Cohort 2 Arm A, Period 1 Day 1 through Day 8 and Period 2 Day -4 through Day 16; Cohort 2 Arm B, Period 1 Day 1 through Day 8 and Period 2 Day -10 through Day 8; Cohort 3, Day 1 through Day 92.

• Change From Baseline in RR Interval

  Change From Baseline in RR Interval Change from baseline in RR interval, measured in milliseconds (ms).

  Cohort 1, Day 1 through Day 19; Cohort 2 Arm A, Period 1 Day 1 through Day 8 and Period 2 Day -4 through Day 16; Cohort 2 Arm B, Period 1 Day 1 through Day 8 and Period 2 Day -10 through Day 8; Cohort 3, Day 1 through Day 92.

• Change From Baseline in PR Interval

  Change From Baseline in PR Interval Change from baseline in PR interval, measured in milliseconds (ms).

  Cohort 1, Day 1 through Day 19; Cohort 2 Arm A, Period 1 Day 1 through Day 8 and Period 2 Day -4 through Day 16; Cohort 2 Arm B, Period 1 Day 1 through Day 8 and Period 2 Day -10 through Day 8; Cohort 3, Day 1 through Day 92.

• Change From Baseline in QRS Duration

  Change From Baseline in QRS Duration Change from baseline in QRS duration, measured in milliseconds (ms).

  Cohort 1, Day 1 through Day 19; Cohort 2 Arm A, Period 1 Day 1 through Day 8 and Period 2 Day -4 through Day 16; Cohort 2 Arm B, Period 1 Day 1 through Day 8 and Period 2 Day -10 through Day 8; Cohort 3, Day 1 through Day 92.

• Change From Baseline in QT Interval

  Change From Baseline in QT Interval Change from baseline in QT interval, measured in milliseconds (ms).

  Cohort 1, Day 1 through Day 19; Cohort 2 Arm A, Period 1 Day 1 through Day 8 and Period 2 Day -4 through Day 16; Cohort 2 Arm B, Period 1 Day 1 through Day 8 and Period 2 Day -10 through Day 8; Cohort 3, Day 1 through Day 92.

• Change From Baseline in QTcF Interval

  Change from baseline in QT interval corrected for heart rate using Fridericia's formula (QTcF), measured in milliseconds (ms).

  Cohort 1, Day 1 through Day 19; Cohort 2 Arm A, Period 1 Day 1 through Day 8 and Period 2 Day -4 through Day 16; Cohort 2 Arm B, Period 1 Day 1 through Day 8 and Period 2 Day -10 through Day 8; Cohort 3, Day 1 through Day 92.

Secondary Outcomes (10)

• Maximum Observed Plasma Concentration of TBD11

  Cohort 1: Day 1 and Day 14. Cohort 3: Day 1 and Day 84.

• Time to Maximum Observed Plasma Concentration of TBD11

  Cohort 1: Day 1 and Day 14. Cohort 3: Day 1 and Day 84.

• Area Under the Plasma Concentration-Time Curve From Time Zero to 24 Hours for TBD11

  Cohort 1: Day 1. Cohort 3: Day 1

• Area Under the Plasma Concentration-Time Curve From Time Zero to the Last Quantifiable Concentration for TBD11

  Cohort 1: Day 14. Cohort 3: Day 84.

• Minimum Plasma Concentration of TBD11

  Cohort 1: Day 14. Cohort 3: Day 84

Study Arms (4)

Cohort 1 (TBD11 or placebo)

EXPERIMENTAL

Participants randomized 3:1 to receiveTBD11 300 mg or matching placebo once daily for up to 14 days

Drug: TBD11 (300 mg); Drug: Placebo

Cohort 2 Arm A

EXPERIMENTAL

Participants receive TBD11 50 mg single dose alone and in combination with itraconazole 200 mg BID loading dose followed by 200 mg QD.

Drug: Itraconazole (200 mg); Drug: TBD11 (50 mg)

Cohort 2 Arm B

EXPERIMENTAL

Participants receive TBD11 up to 300 mg single dose alone and in combination with rifampicin 600 mg QD.

Drug: Rifampicin 600mg; Drug: TBD11 (up to 300 mg)

Cohort 3 (TBD11 or placebo)

EXPERIMENTAL

Participants randomized 2:1 to receive TBD11 up to 300 mg or matching placebo once daily for up to 84 days

Drug: Placebo; Drug: TBD11 (up to 300 mg)

Interventions

TBD11 (300 mg) DRUG

TBD11: TBD11 administered orally at 300 mg

Cohort 1 (TBD11 or placebo)

Placebo DRUG

Matching placebo administered orally according to the cohort-specific dosing schedule.

Cohort 1 (TBD11 or placebo); Cohort 3 (TBD11 or placebo)

Itraconazole (200 mg) DRUG

Itraconazole 200 mg orally once daily, with a 400 mg loading dose on the first day of administration.

Cohort 2 Arm A

Rifampicin 600mg DRUG

Rifampicin 600 mg orally once daily.

Cohort 2 Arm B

TBD11 (50 mg) DRUG

TBD11: TBD11 administered orally at 50 mg

Cohort 2 Arm A

TBD11 (up to 300 mg) DRUG

TBD11: TBD11 administered orally at up to 300 mg

Cohort 2 Arm B; Cohort 3 (TBD11 or placebo)

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• to 55 years of age, inclusive.
• Healthy, as determined by the Investigator through medical history and clinical examination before enrolment.
• Able to understand and comply with trial and site procedures, understand study risks, and provide written informed consent before any trial-specific procedure.
• Able to complete all Screening evaluations and remain in the clinical research facility for required inpatient periods.
• BMI between 18 and 32 kg/m², inclusive, and body weight of at least 50 kg at Screening.
• Resting vital signs within protocol-defined ranges at Screening and Day -1.
• lead ECG consistent with normal cardiac conduction and function at Screening.
• Non-smoker within the previous 90 days, with negative urine cotinine at Screening and no use of tobacco- or nicotine-containing products.
• Screening clinical chemistry, coagulation, complete blood count, and urinalysis within laboratory reference ranges, unless assessed as not clinically significant by the Investigator/designee.
• Negative HBsAg and HCV antibody at Screening.
• Negative IGRA test for TB infection.
• Negative HIV antibody test at Screening.
• Negative urine drug screen and urine alcohol screen at Screening and Day -1.
• For participants assigned female sex at birth: negative urine and serum pregnancy tests at Screening and non-childbearing potential as defined in the protocol.
• For participants assigned male sex at birth who are not sterilized and sexually active with a female partner of childbearing potential: agreement to use condoms from Day -1 through 90 days after the last dose and not donate sperm during the trial and for 90 days after the last dose.

You may not qualify if:

• Current or past clinically significant cardiovascular, cerebrovascular, respiratory, gastrointestinal, haematologic, renal, hepatic, immunologic, metabolic, urologic, neurologic, dermatologic, psychiatric, or other major disease.
• Current or past condition expected to require treatment during the trial with medication known to inhibit or induce CYP3A4.
• Clinically relevant cardiovascular disorder or symptoms suggestive of such disorder.
• Prior history of TB infection or TB disease.
• Current cough lasting more than 2 weeks, fever, night sweats, or unexplained weight loss.
• Close household or repeated living/workspace contact with an individual with active TB in the preceding 12 months.
• History of drug abuse within 1 year before Screening or use of specified hard drugs within 1 year before Screening, unless limited to prescribed opioid or amphetamine medication not currently being taken.
• Surgical or medical condition that may alter absorption, metabolism, or excretion of trial treatment.
• Use of prohibited medications, vitamins, dietary supplements, herbal products, or vaccination within the protocol-defined windows.
• Contraindication to trial interventions or excipients, or clinically significant allergic/anaphylactic reaction to any medication.
• Participation in another investigational drug, vaccine, or device study within 30 days or 5 half-lives, whichever is longer, before Screening and during this trial.
• Any condition that may interfere with informed consent, compliance, interpretation of results, or place the participant at undue risk.
• Blood donation within 2 months before Screening or planned blood donation during the trial or within 12 weeks after the final visit.

Sponsors & Collaborators

• Gates Medical Research Institute: lead
• IQVIA RDS Inc.: collaborator

Study Sites (1)

FARMOVS (Pty) Ltd

Bloemfontein, 9301, South Africa

Location

MeSH Terms

Interventions

Itraconazole; Rifampin

Intervention Hierarchy (Ancestors)

Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Piperazines; Rifamycins; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Lactams, Macrocyclic; Macrocyclic Compounds; Polycyclic Compounds

Study Officials

• Gates MRI

  Gates Medical Research Institute

  STUDY DIRECTOR

Central Study Contacts

Gates MRI

CONTACT

+1-857-702-2108; Clinical.trials@gatesmri.org

Gates MRI

CONTACT

+1-866-789-5757; Clinical.trials@gatesmri.org

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 28, 2026
• First Posted: October 20, 2026
• Study Start: October 16, 2026
• Primary Completion (Estimated): May 30, 2027
• Study Completion (Estimated): May 30, 2027
• Last Updated: October 20, 2026

Record last verified: 2026-10

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: Within 12 months of study completion date.
• Access Criteria: Anonymized participant-level data may be shared with the external research in accordance with trial participant' written and executed informed consent and applicable local regulations. Qualified research may submit a request along with a research proposal to Gates MRI for review. A data sharing agreement must be in place before any clinical trial data are shared. Additional restrictions may apply due to contractual obligations or regulatory constraints.

Locations

ZA (1)