Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of Sutezolid

NCT03199313 | Completed Phase 1 FDA Drug

• 1 other identifier: Sutezolid - CL001
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 1

Brief Summary

This is a randomized, double-blind, placebo-controlled, single ascending dose study conducted at one study center in the United States. Four (4) cohorts of 8 subjects each (6 active and 2 placebo). Subjects will participate in only one cohort. Safety will be assessed throughout the study; serial ECGs and serial blood samples will be collected for the safety and PK assessment of sutezolid. Dose escalation to the next cohort (i.e., dose level) will not take place until the Sponsor, in conjunction with the Principal Investigator, has determined that adequate safety, tolerability and PK from the previous cohort has been demonstrated to permit proceeding to the next cohort. Interim PK analyses will be performed for the dose escalation decisions to reconsider the sampling time points as the study progresses. All samples will be sent for analysis and the bioanalytical lab will be unblinded and only run the analysis on active treatment subjects. Data from the analysis used for the escalation meetings will only include active treatment subjects, and will be blinded by subject. Subjects will be housed in the clinic from at least 24 hours prior (from Day -2), until 48 hours (Day 3) after dosing. Subjects will be contacted via a phone call for follow-up questioning about adverse events 7 days later (Study Day 10).

Conditions

Tuberculosis; Tuberculosis, Pulmonary

Keywords

tuberculosis; TB; Sutezolid; pulmonary tuberculosis

Outcome Measures

Primary Outcomes (1)

• Safety and tolerability of single oral doses of sutezolid in healthy adult subjects evaluated by Treatment Emergent Adverse Events (TEAEs)

  Safety will be evaluated by Treatment Emergent Adverse Events (TEAEs) following doses of sutezolid or placebo

  Days 0-10

Secondary Outcomes (3)

• Pharmacokinetics (PK) of single oral doses of sutezolid using Cmax

  Days 0-10

• Pharmacokinetics (PK) of single oral doses of sutezolid using AUC

  Days 0-10

• Pharmacokinetics (PK) of single oral doses of sutezolid using Tmax

  Days 0-10

Study Arms (10)

Cohort 1 Sentinel Group 1 - Active

ACTIVE COMPARATOR

N = 2, Initial dosing of Cohort 1 with 300 mg sutezolid or matching placebo, dosed 24 hours before the rest of Cohort 1 Group 2

Drug: Sutezolid

Cohort 1 Sentinel Group 1 - Placebo

PLACEBO COMPARATOR

N = 1, Initial dosing of Cohort 1 with 300 mg sutezolid or matching placebo, dosed 24 hours before the rest of Cohort 1 Group 2

Drug: Placebo

Cohort 1 Sentinel Group 2 - Active

ACTIVE COMPARATOR

N = 4, Secondary dosing of Cohort 1 with 300 mg sutezolid or matching placebo, dosed 24 hours after the rest of Cohort 1 Group 1

Drug: Sutezolid

Cohort 1 Sentinel Group 2 - Placebo

PLACEBO COMPARATOR

N = 1, Secondary dosing of Cohort 1 with 300 mg sutezolid or matching placebo, dosed 24 hours after the rest of Cohort 1 Group 1

Drug: Placebo

Cohort 2 - Active

ACTIVE COMPARATOR

N = 6, 600mg sutezolid or matching placebo

Drug: Sutezolid

Cohort 2 - Placebo

PLACEBO COMPARATOR

N = 2, 600mg sutezolid or matching placebo

Drug: Placebo

Cohort 3 - Active

ACTIVE COMPARATOR

N = 6, 1200 mg sutezolid or matching placebo

Drug: Sutezolid

Cohort 3 - Placebo

PLACEBO COMPARATOR

N = 2, 1200 mg sutezolid or matching placebo

Drug: Placebo

Cohort 4 - Active

ACTIVE COMPARATOR

N = 6, 1800 mg sutezolid or matching placebo

Drug: Sutezolid

Cohort 4 - Placebo

PLACEBO COMPARATOR

N = 2, 1800 mg sutezolid or matching placebo

Drug: Placebo

Interventions

Sutezolid DRUG

Sutezolid supplied as tablets and matching placebo for oral administration.

Also known as: PNU-100480

Cohort 1 Sentinel Group 1 - Active; Cohort 1 Sentinel Group 2 - Active; Cohort 2 - Active; Cohort 3 - Active; Cohort 4 - Active

Placebo DRUG

Matching Sutezolid placebo

Also known as: Placebo Oral Tablet

Cohort 1 Sentinel Group 1 - Placebo; Cohort 1 Sentinel Group 2 - Placebo; Cohort 2 - Placebo; Cohort 3 - Placebo; Cohort 4 - Placebo

Eligibility Criteria

• Age: 19 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Subject understands study procedures and provides written, informed consent prior to all trial-related procedures.
• Healthy adult male and females of non-childbearing potential, 19 to 50 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 study start), must agree to the following during study participation and for 90 days following the last administration of study 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 study start.
• 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 study start.

You may not qualify if:

• Be able to comply with the protocol and the assessments therein, including all restrictions.
• Is willing and able to remain in the study unit for the entire duration of the assigned confinement period and receive a phone call for follow-up questioning about AEs.
• Subjects will be excluded from the study if there is evidence of any of the following criteria at screening or check-in, as appropriate.
• Medical History
• History or presence of significant cardiovascular, pulmonary, hepatic, renal, hematological, gastrointestinal, endocrine, immunologic, dermatologic, neurological, or psychiatric disease as determined by the Investigator to be clinically relevant.
• 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 subject by their participation in the study.
• Surgery within the past 90 days prior to dosing as determined by the Investigator to be clinically relevant, or any history of cholecystectomy.
• History or presence of alcoholism or drug abuse within the past 2 years as determined by the Investigator to be clinically relevant.
• History of sensitivity or contraindication to use of linezolid or any study investigational products.
• Female subjects who are pregnant or lactating.
• Seated blood pressure is less than 90/40 mmHg or greater than 140/90 mmHg at screening.
• Heart rate is lower than 40 bpm or higher than 99 bpm at screening.
• Any clinically significant electrocardiogram abnormality at Screening (as deemed by decision of the Investigator and the Sponsor's Medical Monitor).
• NOTE: The following can be considered not clinically significant without consulting the Sponsor's Medical Monitor:
• Mild first degree A-V block (P-R interval \<0.23 sec)

Sponsors & Collaborators

• Global Alliance for TB Drug Development: lead

Study Sites (1)

Worldwide Clinical Trials

San Antonio, Texas, 78217, United States

Location

MeSH Terms

Conditions

Tuberculosis; Tuberculosis, Pulmonary

Interventions

PNU-100480

Condition Hierarchy (Ancestors)

Mycobacterium Infections; Actinomycetales Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Respiratory Tract Infections; Lung Diseases; Respiratory Tract Diseases

Study Officials

• Paul Bruinenberg, MD

  Global Alliance for TB Drug Development

  STUDY DIRECTOR

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: June 23, 2017
• First Posted: June 26, 2017
• Study Start: September 26, 2017
• Primary Completion: December 16, 2017
• Study Completion: December 16, 2017
• Last Updated: February 8, 2018

Record last verified: 2018-02

Locations

US (1)