Evaluation of the Safety, Tolerability, PK of TBAJ-587 in Healthy Adults

NCT04890535 | Completed Phase 1

• 1 other identifier: TBAJ-587-CL001
• Study Type: interventional
• Target: 106
• Locations: 1 country
• Sites: 1

Brief Summary

Phase 1, Partially Blinded, Placebo-Controlled, Randomized, Combined Single Ascending Dose with Food Effect Cohort Trial (Part 1) and Multiple Ascending Dose Trial (Part 2) to Evaluate the Safety, Tolerability, and PK of TBAJ-587 in Healthy Adults

Conditions

Tuberculosis

Keywords

Phase I

Outcome Measures

Primary Outcomes (2)

• Number of Participants with Treatment-Related Adverse Events in the Single Ascending Dose (SAD) population

  Subjects will be monitored for any adverse events from the signing of the consent form until the end-of-study visit. The Investigator or a Sub-Investigator will assess its relationship to the study drug.

  from date of the start of treatment through completion of clinical procedures on Day 126

• Number of Participants with Treatment-Related Adverse Events in the Multiple Ascending Dose (MAD) population

  Subjects will be monitored for any adverse events from the signing of the consent form until the end-of-study visit. The Investigator or a Sub-Investigator will assess its relationship to the study drug.

  from date of the start of treatment through completion of clinical procedures on Day 168

Secondary Outcomes (4)

• Pharmacokinetics, Maximum concentration (Cmax), of TBAJ-587 and metabolites

  Day(D)1: 0,0.5,1,1.5,2,3,4,5,6,7,8,10,12,16; D2: 24,28,32,36,40,44; D3: 48,54,60,66; D4: 72,78,84,90; D5: 96,108; D6: 120,132; D7: 144,156; D8: 168; D14: 0.5,1,2,3,4,5,6,7,8,12,16,24; D28: 0.5,1,2,3,4,5,6,7,8,12,16,24,36

• Pharmacokinetics, Time of maximum concentration (Tmax), of TBAJ-587 and metabolites

  Day(D)1: 0,0.5,1,1.5,2,3,4,5,6,7,8,10,12,16; D2: 24,28,32,36,40,44; D3: 48,54,60,66; D4: 72,78,84,90; D5: 96,108; D6: 120,132; D7: 144,156; D8: 168; D14: 0.5,1,2,3,4,5,6,7,8,12,16,24; D28: 0.5,1,2,3,4,5,6,7,8,12,16,24,36

• Pharmacokinetics, Area under the concentration-time curve (AUC), of TBAJ-587 and metabolites

  Day(D)1: 0,0.5,1,1.5,2,3,4,5,6,7,8,10,12,16; D2: 24,28,32,36,40,44; D3: 48,54,60,66; D4: 72,78,84,90; D5: 96,108; D6: 120,132; D7: 144,156; D8: 168; D14: 0.5,1,2,3,4,5,6,7,8,12,16,24; D28: 0.5,1,2,3,4,5,6,7,8,12,16,24,36

• Effect of a high-calorie, high-fat meal on the pharmacokinetics of TBAJ-587

  Day 1: 0, 0.5, 1, 1,5, 2, 3, 4, 5, 6, 7, 8, 10, 12, 16; Day 2: 24, 28, 32, 36, 40, 44; Day 3: 48, 54, 60, 66; Day 4: 72, 78, 84, 90; Day 5: 96, 108; Day 6: 120, 132; Day 7: 144, 156; Day 8: 168

Study Arms (4)

Single Ascending Dose 25 - 800 mg

ACTIVE COMPARATOR

single dose of TBAJ-587

Drug: TBAJ-587

Single Ascending Dose 25 - 800 mg placebo

PLACEBO COMPARATOR

single dose of placebo

Drug: Placebo

Multiple Ascending Dose 50 - 200 mg

ACTIVE COMPARATOR

28 days dose of TBAJ-587

Drug: TBAJ-587

Multiple Ascending Dose 50 - 200 mg Placebo

PLACEBO COMPARATOR

28 days dose of placebo

Drug: Placebo

Interventions

TBAJ-587 DRUG

oral suspension

Multiple Ascending Dose 50 - 200 mg; Single Ascending Dose 25 - 800 mg

Placebo DRUG

matching placebo oral suspension for TBAJ-587

Multiple Ascending Dose 50 - 200 mg Placebo; Single Ascending Dose 25 - 800 mg placebo

Eligibility Criteria

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

You may qualify if:

• Provide written, informed consent prior to all trial-related procedures.
• Healthy adult male and females of non-childbearing potential, 18-64 years of age (inclusive) at the time of screening.
• Body mass index (BMI) ≥ 18.5 and ≤ 32.0 (kg/m2) and a body weight of no less than 50.0 kg.
• No use of tobacco or nicotine containing products (including smoking cessation products), for a minimum of 6 months prior to dosing.
• Females of non-childbearing potential, having undergone one of the following sterilization procedures at least 6 months prior to dosing:
• Hysteroscopic sterilization
• Bilateral tubal ligation or bilateral salpingectomy
• Hysterectomy
• Bilateral oophorectomy or be postmenopausal with amenorrhea for at least 1 year prior to the first dose with serum
• Follicle-stimulating hormone (FSH) levels consistent with postmenopausal status at screening.
• Non-vasectomized males (or males vasectomized less than 120 days prior to trial start), must agree to the following during trial participation and for 90 days following the last administration of trial drug:
• Use a condom with spermicide while engaging in sexual activity or be sexually abstinent
• Not donate sperm during this time.
• In the event the sexual partner is surgically sterile, use of a condom with spermicide is not necessary.
• None of the restrictions listed above are required for vasectomized males whose procedure was performed more than 120 days prior to trial start.

You may not qualify if:

• Participant understands trial procedures and provides written informed consent for the trial.
• Be able to comply with the protocol and the assessments therein, including all restrictions.
• Is willing and able to remain in the trial unit for the entire duration of the assigned confinement period and return for outpatient visits.
• If enrolled in Part 1 and assigned to the fasted/fed cohort, is willing and able to consume the entire high-calorie, high-fat breakfast meal in the timeframe required.
• Has negative Quantiferon test during the screening. -
• Participants will be excluded from the trial if there is evidence of any of the following criteria at screening or check-in, as appropriate.
• History or presence of significant cardiovascular abnormalities, Heart Murmur, pulmonary, hepatic, renal, haematological, gastrointestinal, endocrine, immunologic, dermatologic, neurological, or psychiatric disease as determined by the Investigator to be clinically relevant.
• Any musculoskeletal abnormality (severe tenderness with marked impairment of activity) or musculoskeletal toxicity (frank necrosis).
• History of any illness that, in the opinion of the Investigator, might confound the results of the trial or poses an additional risk to the participant by their participation in the trial.
• Surgery within the past 90 days prior to dosing or other previous surgery 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.
• Female participants who are pregnant or lactating.
• Positive results for the urine drug/alcohol breath screen at screening or check-in.
• Positive urine cotinine at screening or check-in.
• Participants with the following laboratory abnormalities at screening:

Sponsors & Collaborators

• Global Alliance for TB Drug Development: lead
• QPS Holdings LLC: collaborator

Study Sites (1)

QPS Netherlands B.V.

Groningen, Netherlands

Location

Related Publications (2)

• Leding AAM, Bruinenberg P, Conradie A, Nedelman J, Lombardi A, Hickman D, Simonsson USH. Population pharmacokinetics of TBAJ-587 and its main metabolites-Evaluation of different loading dose strategies and early dose selection. Br J Clin Pharmacol. 2025 Nov 19. doi: 10.1002/bcp.70333. Online ahead of print.

  PMID: 41255184 DERIVED

• Komm OD, Tyagi S, Garcia A, Almeida D, Chang Y, Li S-Y, Castillo JR, Converse PJ, Black T, Fotouhi N, Nuermberger EL. Contribution of telacebec to novel drug regimens in a murine tuberculosis model. Antimicrob Agents Chemother. 2025 Jan 31;69(1):e0096224. doi: 10.1128/aac.00962-24. Epub 2024 Dec 9.

  PMID: 39651910 DERIVED

MeSH Terms

Conditions

Tuberculosis

Condition Hierarchy (Ancestors)

Mycobacterium Infections; Actinomycetales Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections

Study Officials

• Paul Bruinenberg, MD, MBA

  Global Alliance for TB Drug Development

  STUDY CHAIR

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: February 19, 2021
• First Posted: May 18, 2021
• Study Start: December 1, 2020
• Primary Completion: February 27, 2023
• Study Completion: February 27, 2023
• Last Updated: May 19, 2023

Record last verified: 2023-05

Locations

NL (1)