TuberculosisPhase 1NCT01768273
Evaluation of the Pharmacokinetic Interaction Between PA-824 and Midazolam
A Phase 1 study testing Midazolam and PA-824 in people with Tuberculosis, run by Global Alliance for TB Drug Development at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 19 to 50 yearsHealthy volunteers can take part
- Conditions the study is for
- Tuberculosis
- What is being tested?
- Midazolam and PA-824
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 14 participants
- Where
- 1 siteUnited States
- Study dates
- Dec 2009to Apr 2010
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 19 to 50 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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.
Who cannot join
- 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:
Show all 41Show fewer
- 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)
- At either Screening or the pre-dose read before the first dose, a QTcB (Bazett's correction) >450ms for men and women, calculated from the average of triplicate reads collected at the screening and predose sitting.
- At either Screening or the pre-dose read before the first dose, a QTcF (Fridericia's correction) >450ms for men and women, calculated from the average of triplicate reads collected at the screening and predose sitting.
- History of hypokalemia or hypomagnesemia.
- History or presence of alcoholism or drug abuse within the past 2 years (as deemed by the Principal Investigator).
- Use of alcohol within 72 hours prior to dosing.
- Significant history of drug and/or food allergies (as deemed by the Principal Investigator).
- For women, subject is pregnant (positive test for serum HCG at Screening or Check-in), breastfeeding or planning to conceive a child within 30 days of cessation of treatment.
- For males, planning to father a child within 12 weeks of cessation of treatment.
- History of lens opacity or evidence of lens opacity on slit lamp ophthalmologic examination.
- Specific Treatments
- Any contraindication to the use of nitroimidazoles, or prior treatment with PA-824 or OPC-67683.
- Use of any systemic or topical prescription medication within 14 days prior to dosing or during the study, except hormonal contraceptives in women.
- Use of any systemic or over-the-counter medication including vitamins, herbal preparations, antacids, cough and cold remedies, etc., within 7 days prior to dosing or during the study treatment periods.
- Use of any drugs or substances within 30 days prior to dosing, known to be strong inhibitors or inducers of cytochrome P450 enzymes (including quinidine, tyramine, ketoconazole, testosterone, quinine, gestodene, metyrapone, phenelzine, doxorubicin, troleandomycin, cyclobenzaprine, erythromycin, cocaine, furafylline, cimetidine, dextromethorphan, etc.) or known to prolong the QT interval (including amiodarone, bepridil chloroquine, chlorpromazine, cisapride, clarithromycin, disopyramide dofetilide, domperidone, droperidol, erythromycin, halofantrine, haloperidol, ibutilide, levomethadyl, mesoridazine, methadone, pentamidine, pimozide, procainamide, quinidine, quinolones, sotalol, sparfloxacin, thioridazine,) or barbiturates, opiates, or phenothiazines.
- Use of any therapeutic agents known to alter any major organ function (e.g., barbiturates, opiates, phenothiazines, cimetidine, etc.) within 30 days prior to dosing.
- Consumption of products containing grapefruit within 10 days prior to dosing.
- Any special dietary changes during the 30 days prior to dosing, as deemed by the Principal Investigator in consultation with the Sponsor Medical Monitor.
- Any strenuous exercise within 7 days of Check-in, as deemed by the Principal Investigator in consultation with the Sponsor Medical Monitor.
- Donation of whole blood or significant loss of blood within 56 days prior to dosing.
- Plasma donation within 7 days prior to dosing.
- Participation in another interventional clinical trial within 30 days prior to dosing.
- Based on Lab Abnormalities
- Any serum creatinine or BUN measure beyond the upper limit of the normal range at Screening or Check-in. Individual values may be discussed with the Sponsor Medical Monitor.
- Hemoglobin < 12.0 g/dL at the screening visit.
- Positive Screening test for HCV, HBV, or HIV.
- Any other factor which suggests to the Principal Investigator that the subject should not participate in the study.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Phase 1, Open-label, Multi-Dose Study to Assess Pharmacokinetic Interaction Between PA-824 and Midazolam
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.
Read the detailed description
This study is an open-label, fixed sequence design. 14 subjects will receive a single dose of 2 mg midazolam, followed by a 2-day wash-out. Following the wash-out, all subjects will receive PA-824 once daily for 14 days. All patients will receive a single dose of 2 mg midazolam on the 14th day of PA-824 dosing. This study will evaluate 400 mg PA-824.
- Conditions
- Tuberculosis
- Being tested
- Midazolam, PA-824
- Keywords
- PA-824,, midazolam, drug-drug interaction, pharmacokinetics, pretomanid, CL-006
- Medical subject headings
- Tuberculosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MidazolamDrug
Also called Dormicum, Hypnovel, Versed
PA-824Drug
| Study group | Role | What they receive |
|---|---|---|
| Midazolam and 824 | Experimental | 2 mg midazolam (oral syrup) Day 1 and Day 17. 400 mg PA-824 once daily Day 4 - 17. Receives: Drug: Midazolam; Drug: PA-824 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: 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)
Measured: Day 108
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Jan 2013 (estimated)
- Study startDec 2009
- Primary completionJan 2010
- Study completionApr 2010
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for TuberculosisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 14 participants (actual)
Sponsor and investigators
- Lead sponsor
- Global Alliance for TB Drug Development
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Scott Rasmussen, M.D., Principal investigator, MDS Pharma Services
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01768273
- Sponsor's protocol ID
- PA-824-CL-006
- Status last verified
- Sep 2019
- First submitted
- 7 Jan 2013
- Last updated
- 12 Sep 2019
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 12 Sep 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1, Open-label, Multi-Dose Study to Assess Pharmacokinetic Interaction Between PA-824 and Midazolam
- ClinicalTrials.gov ID
- NCT01768273
- Acronym / sponsor ID
- PA-824-CL-006
- Conditions
- Tuberculosis
- Keywords
- PA-824,, midazolam, drug-drug interaction, pharmacokinetics, pretomanid, CL-006
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 14 participants (actual)
- Lead sponsor
- Global Alliance for TB Drug DevelopmentUniversity, hospital or other
- Study start
- Dec 2009
- Primary completion
- Jan 2010 (actual)
- Study completion
- Apr 2010 (actual)
- First posted
- 15 Jan 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
This study is an open-label, fixed sequence design. 14 subjects will receive a single dose of 2 mg midazolam, followed by a 2-day wash-out. Following the wash-out, all subjects will receive PA-824 once daily for 14 days. All patients will receive a single dose of 2 mg midazolam on the 14th day of PA-824 dosing. This study will evaluate 400 mg PA-824.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Midazolam and 824 | Experimental | Drug: Midazolam, Drug: PA-8242 mg midazolam (oral syrup) Day 1 and Day 17. 400 mg PA-824 once daily Day 4 - 17. |
Who may qualify
- Ages
- 19 to 50 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (6 listed)
- 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.
Key exclusion criteria (41 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MidazolamAlso: Dormicum, Hypnovel, Versed | Drug | Midazolam and 824 |
| PA-824 | Drug | Midazolam and 824 |
Primary outcome
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.
Time frame: Day 18
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).
To evaluate the safety and tolerability of PA-824 when given with midazolam.
Time frame: Day 108
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)
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Sep 2019.
- Related InfoLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Scott Rasmussen, M.D. principal investigator
MDS Pharma Services
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Midazolam and PA-824 in people with Tuberculosis, run by Global Alliance for TB Drug Development at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 41 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 12 Sep 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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. (time frame: Day 18). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Sep 2019.