Evaluation of the Pharmacokinetic Interaction Between PA-824 and Midazolam

NCT01768273 | Completed Phase 1

• 1 other identifier: PA-824-CL-006
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to determine the safety and tolerability of PA-824 when given with a single dose of midazolam, and to determine whether PA-824 inhibits CYP3A to a clinically important degree as measured by the effect of PA-824 on the pharmacokinetics of midazolam, a known CYP3A substrate.

Conditions

Tuberculosis

Keywords

PA-824,; midazolam; drug-drug interaction; pharmacokinetics; pretomanid; CL-006

Outcome Measures

Primary Outcomes (2)

• Evaluate the effects of multiple-dose administration of PA-824 on the pharmacokinetics of midazolam, a sensitive probe substrate and representative compound for drugs metabolized by CYP3A enzymes.

  The PK parameters to be calculated for midazolam and 1-hydroxy midazolam include area under the curve \[AUC(0-t) and AUC(0-inf)\], maximum observed concentration (Cmax), time to maximum observed plasma concentration (Tmax), half-life (t1/2), and apparent terminal elimination rate constant (Kel).

  Day 18

• To evaluate the safety and tolerability of PA-824 when given with midazolam.

  Safety assessments include clinical laboratory assessments, vital signs including respiration rates, electrocardiograms (ECGs), physical examinations, ophthalmology examinations, including visual acuity tests and slit lamp examinations, and monitoring of adverse events (AEs)

  Day 108

Study Arms (1)

Midazolam and 824

EXPERIMENTAL

2 mg midazolam (oral syrup) Day 1 and Day 17. 400 mg PA-824 once daily Day 4 - 17.

Drug: Midazolam; Drug: PA-824

Interventions

Midazolam DRUG

Also known as: Dormicum, Hypnovel, Versed

Midazolam and 824

PA-824 DRUG

Midazolam and 824

Eligibility Criteria

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

You may qualify if:

• Have the ability to understand the requirements of the study, have provided written informed consent (as evidenced by signature on an informed consent document approved by an IRB), and agree to abide by the study restrictions.
• Be healthy non-tobacco/nicotine using (6-month minimum) adult subjects, 19 to 50 years of age, inclusive.
• Be medically healthy subjects with clinically insignificant Screening results (among laboratory profiles, medical histories, ECGs, or physical exam), as deemed by the Principal Investigator.
• Have a body mass index of 18 to 29.
• Have negative urine test results for alcohol and drugs of abuse such as amphetamines, cannabinoids, and cocaine metabolites at both Screening and Check-in.
• Agree to follow the requirements set forth in the protocol regarding pregnancy controls and donation of sperm, blood, or blood components.

You may not qualify if:

• Medical History
• Any clinically significant (as deemed by the Principal Investigator) history, acute illness (resolved within 4 weeks of screening), or presence of cardiovascular, pulmonary, hepatic, renal, hematologic, gastrointestinal (including eating disorders), endocrine, metabolic, immunologic, dermatologic, neurologic, psychological, or psychiatric disease.
• History of peptic ulcer disease, gastritis, esophagitis, or gastroesophageal reflux disease.
• History of any clinically significant cardiac abnormality (as deemed by the Principal Investigator).
• Any clinically significant ECG abnormality at Screening (as deemed by the Principal Investigator and the Sponsor's Medical Monitor)
• Note: the following can be considered not clinically significant without consulting Sponsor's Medical Monitor:
• Heart rate ≥50 beats per minute (sinus bradycardia with heart rate between 45 and 49, inclusive, is acceptable only in younger athletic subjects)
• Mild first degree A-V block (P-R interval \<0.23 sec)
• Right or left axis deviation
• Incomplete right bundle branch block
• Isolated left anterior fascicular block (left anterior hemiblock) in younger athletic subjects
• History of prolonged QT interval.
• 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 or CHF or terminal cancer)
• Resting pulse rate \< 40 or \> 100 bpm at Screening.
• At Screening blood pressure greater than 140/90 mm Hg or below 95/65 mm Hg (supine, after a minimum 5-minute supine rest)

Sponsors & Collaborators

• Global Alliance for TB Drug Development: lead

Study Sites (1)

MDS Pharma Services

Lincoln, Nebraska, 68502, United States

Location

Related Links

• Related Info

MeSH Terms

Conditions

Tuberculosis

Interventions

Midazolam; pretomanid

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Benzodiazepines; Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Scott Rasmussen, M.D.

  MDS Pharma Services

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 7, 2013
• First Posted: January 15, 2013
• Study Start: December 1, 2009
• Primary Completion: January 1, 2010
• Study Completion: April 1, 2010
• Last Updated: September 12, 2019

Record last verified: 2019-09

Locations

US (1)