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Infection, Human Immunodeficiency VirusPhase 1NCT02411435

Effect of Rifampin (RIF) on the Pharmacokinetics (PK) of Oral Cabotegravir (CAB) in Healthy Subjects

A Phase 1 study testing CAB and RIF in people with Infection, Human Immunodeficiency Virus, run by ViiV Healthcare at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

CAB is an integrase inhibitor that is currently in Phase 2 clinical trials for the treatment and prevention of human immunodeficiency virus-1 (HIV-1) infection. RIF, a rifamycin used for treatment of tuberculosis (common co-infection in HIV-infected subjects), is a known inducer of uridine diphosphate… Read more about this study

Who is it for?
Ages 18 to 65 yearsHealthy volunteers can take part
Conditions the study is for
Infection, Human Immunodeficiency Virus
What is being tested?
CAB and RIF
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
15 participants
Where
1 siteUnited States
Study dates
Jul 2015to Sep 2015
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 18 to 65 years
  • All sexes
  • Healthy volunteers accepted
  • Adult, Older adult

Who may be able to join

  • Males and females between 18 and 65 years of age inclusive, at the time of signing the informed consent.
  • Healthy as determined by a responsible and experienced physician, based on a medical evaluation including medical history, physical examination, laboratory tests and cardiac monitoring.
  • Body weight >=50 kilogram (kg) and body mass index (BMI) within the range 18.5 - 31.0 kg/meter square (m^2) (inclusive).
  • Male or female - A female subject is eligible to participate if she is not pregnant (as confirmed by a negative serum human chorionic gonadotrophin [hCG] test), not lactating, and at least one of the following conditions applies: a) Non-reproductive potential defined as: Pre-menopausal females with one of the following [for this definition, "documented" refers to the outcome of the investigator's/designee's review of the subject's medical history for study eligibility, as obtained via a verbal interview with the subject or from the subject's medical records]: Documented tubal ligation, Documented hysteroscopic tubal occlusion procedure with follow-up confirmation of bilateral tubal occlusion, Hysterectomy, Documented Bilateral Oophorectomy; b) Postmenopausal defined as 12 months of spontaneous amenorrhea [in questionable cases a blood sample with simultaneous follicle stimulating hormone (FSH) and estradiol levels consistent with menopause >40 milli-international units per mililiter (MIU/mL) and estradiol <40 picogram/milliliter (pg/mL) (<147 picomoles/liter [pmol/L]) is confirmatory]; c) Reproductive potential and agrees to follow one of the options listed in the GlaxoSmithKline (GSK) Modified List of Highly Effective Methods for Avoiding Pregnancy in Females of Reproductive Potential (FRP) requirements from 30 days prior to the first dose of study medication and until after the last dose of study medication and completion of the follow-up visit.
  • Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the consent form and in the protocol.
  • Alanine aminotransferase (ALT), alkaline phosphatase and bilirubin <=1x upper limit of normal (ULN) (isolated bilirubin >1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin <35%).

Who cannot join

  • Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
  • History of clinically significant cardiovascular disease including: a) Exclusion criteria for screening ECG (a single repeat is allowed for eligibility determination): Heart rate <45 and >100 beats per minute for male subjects and <50 and >100 beats per minute for female subjects, QRS duration >120 millisecond (msec), and QT interval corrected by Fridericia's formula (QTcF) >450 msec; b) Evidence of previous myocardial infarction (pathologic Q waves, S-T segment changes (except early repolarization); c) History/evidence of symptomatic arrhythmia, angina/ischemia, coronary artery bypass grafting (CABG) surgery or percutaneous transluminal coronary angioplasty (PCTA) or any clinically significant cardiac disease; d) Any conduction abnormality (including but not specific to left or right complete bundle branch block, atrioventricular (AV) block [2nd degree (type II) or higher], Wolf Parkinson White [WPW] syndrome) which in the opinion of the principal Investigator and GSK Medical Monitor, will interfere with the safety for the individual subject; e) Sinus pauses >3 seconds; f) Any significant arrhythmia which, in the opinion of the principal Investigator and GSK Medical Monitor, will interfere with the safety for the individual subject; g) Non-sustained (>=3 consecutive ventricular ectopic beats) or sustained ventricular tachycardia.
  • Subjects must abstain from taking prescription or non-prescription drugs (including vitamins and dietary or herbal supplements), within 7 days (or 14 days if the drug is a potential enzyme inducer) or 5 half-lives (whichever is longer) prior to the first dose of study medication until completion of the follow-up visit, unless in the opinion of the Investigator and sponsor the medication will not interfere with the study.
  • History of regular alcohol consumption within 6 months of the study defined as: An average weekly intake of >14 drinks for males or >7 drinks for females. One drink is equivalent to 12 grams of alcohol: 12 ounces (360 mL) of beer, 5 ounces (150 mL) of wine or 1.5 ounces (45 mL) of 80 proof distilled spirits.
  • A history of regular use of tobacco, or nicotine-containing products within 30 days prior to screening.
  • History of sensitivity to any of the study medications, or components thereof or a history of drug or other allergy that, in the opinion of the investigator or Medical Monitor, contraindicates their participation.
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  • Presence of Hepatitis B surface antigen (HBsAg), positive Hepatitis C antibody test result at screening or within 3 months prior to first dose of study treatment. Hepatitis B core antibody (HBcAb) with negative hepatitis B surface antibody should also be excluded.
  • A positive pre-study drug/alcohol screen.
  • A positive test for HIV antibody.
  • Where participation in the study would result in donation of blood or blood products in excess of 500 mL within a 56 day period.
  • The subject has participated in a clinical trial and has received an investigational product within the following time period prior to the first dosing day in the current study: 30 days, 5 half-lives or twice the duration of the biological effect of the investigational product (whichever is longer).
  • Exposure to more than four new chemical entities within 12 months prior to the first dosing day.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • GSK Investigational Site

    Overland Park, Kansas, 66211

Other trials in United States

About this study

Official title: Phase I, Single-center, Open Label, Fixed-sequence Cross-over Study to Evaluate the Effect of Rifampin on the Pharmacokinetics of Oral Cabotegravir in Healthy Subjects

CAB is an integrase inhibitor that is currently in Phase 2 clinical trials for the treatment and prevention of human immunodeficiency virus-1 (HIV-1) infection. RIF, a rifamycin used for treatment of tuberculosis (common co-infection in HIV-infected subjects), is a known inducer of uridine diphosphate (UDP)-glucuronosyltransferases (UGTs) and Cytochrome P450 3A4 (CYP3A4). CAB is primarily metabolized via UGT1A1 and UGT1A9, thus a drug interaction between CAB and RIF is possible. This study will be a phase I, single-center, open label, fixed-sequence cross-over study to compare the single dose PK of CAB oral 30 milligrams (mg) when co-administered with RIF 600 mg once daily at steady-state to those of CAB oral 30 mg administered alone. Fifteen subjects are planned to be enrolled to obtain 12 evaluable subjects for this study.

Being tested
CAB, RIF
Keywords
rifampin, drug interaction, pharmacokinetics, cabotegravir
Medical subject headings
Infections, Acquired Immunodeficiency Syndrome

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • CABDrug

    CAB 30 mg as 1 tablet will be administered orally with 240 mL of water in the fasted state.

  • RIFDrug

    RIF 600 mg as 2 capsules of 300 mg will be administered orally with 240 mL of water in the fasted state.

Study groups in NCT02411435
Study groupRoleWhat they receive
Treatment A(CAB 30mg)+B (RIF 600mg)+C (CAB 30mg and RIF 600mg)ExperimentalSubjects will receive a single dose of CAB 30 mg on day 1. Subjects will then receive RIF 600 mg once daily on days 8-28 with co-administration of a single dose of CAB 30 mg on day 21.
Receives: Drug: CAB; Drug: RIF

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Plasma CAB maximum observed concentration after single dose administration (Cmax)

    Plasma PK samples collected at the following time points: Period 1 pre-dose (within 15 minutes prior to dosing), 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48 (Day 3), 72 (Day 4), 120 (Day 6), 168 hours post dose. Period 3 pre-dose Day 21 (within 15 minutes prior to dosing), 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48 (Day 3), 72 (Day 4), 120 (Day 6), 168 hours (Day 8) post dose.

    Measured: Days 1, 2, 3, 4, 6, 8, 21, 22, 23, 24, 26, and 28

  2. Plasma CAB area under the concentration versus time from time zero to infinity after single dose administration (AUC(0-∞))

    Plasma PK samples collected at the following time points: Period 1 pre-dose (within 15 minutes prior to dosing), 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48 (Day 3), 72 (Day 4), 120 (Day 6), 168 hours post dose. Period 3 pre-dose Day 21 (within 15 minutes prior to dosing), 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48 (Day 3), 72 (Day 4), 120 (Day 6), 168 hours (Day 8) post dose.

    Measured: Days 1, 2, 3, 4, 6, 8, 21, 22, 23, 24, 26, and 28

Secondary outcomes (9)

  1. Plasma CAB concentration at 24 hours post dose (C24)

    Plasma PK samples collected at Period 1 24 hours post dose and at Period 3 24 hours post dose will be used to measure plasma CAB C24.

    Measured: Days 2 and 22

  2. Plasma CAB AUC from time zero to last time point with measurable concentration after single dose administration (AUC (0-t))

    Plasma PK samples collected at the following time points: Period 1 pre-dose (within 15 minutes prior to dosing), 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48 (Day 3), 72 (Day 4), 120 (Day 6), 168 hours post dose. Period 3 pre-dose Day 21 (within 15 minutes prior to dosing), 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48 (Day 3), 72 (Day 4), 120 (Day 6), 168 hours (Day 8) post dose.

    Measured: Days 1, 2, 3, 4, 6, 8, 21, 22, 23, 24, 26, and 28

  3. Plasma CAB time of occurrence of Cmax (tmax) and terminal phase half-life (t1/2)

    Plasma PK samples collected at the following time points: Period 1 pre-dose (within 15 minutes prior to dosing), 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48 (Day 3), 72 (Day 4), 120 (Day 6), 168 hours post dose. Period 3 pre-dose Day 21 (within 15 minutes prior to dosing), 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48 (Day 3), 72 (Day 4), 120 (Day 6), 168 hours (Day 8) post dose.

    Measured: Days 1, 2, 3, 4, 6, 8, 21, 22, 23, 24, 26, and 28

  4. Plasma CAB apparent clearance following oral dosing (CL/F)

    Plasma PK samples collected at the following time points: Period 1 pre-dose (within 15 minutes prior to dosing), 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48 (Day 3), 72 (Day 4), 120 (Day 6), 168 hours post dose. Period 3 pre-dose Day 21 (within 15 minutes prior to dosing), 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48 (Day 3), 72 (Day 4), 120 (Day 6), 168 hours (Day 8) post dose.

    Measured: Days 1, 2, 3, 4, 6, 8, 21, 22, 23, 24, 26, and 28

  5. Number of subjects with adverse events (AEs) as a measure of safety and tolerability

    AEs will be collected from the start of study treatment until the follow-up contact

    Measured: Up to 42 days

  6. Concurrent medication as a measure of safety and tolerability

    Concurrent medication will be reviewed from the start of study treatment until the follow-up contact.

    Measured: Up to 42 days

  7. Clinical laboratory screens as a measure of safety and tolerability

    Haematology, clinical chemistry, urinalysis and additional parameters will be tested.

    Measured: Day -1, 8, 13, 20, 23, 25, 28, and follow-up (up to Day 42)

  8. Electrocardiogram (ECG) as a measure of safety and tolerability

    Measured: Day 1, 20, 21, and 23

  9. Vital signs assessments as a measure of safety and tolerability

    Measured: Day 1, 8, 20, 21, 25, 26, 28, and follow-up (up to Day 42)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted8 Apr 2015 (estimated)
  2. Study startJul 2015
  3. Primary completionSep 2015
  4. Study completionSep 2015

Resources

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
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
15 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02411435
Sponsor's protocol ID
117010
Status last verified
Jan 2016
First submitted
2 Apr 2015
Last updated
6 Jan 2016
Results posted
No
Data monitoring committee
No

Publications

  • Ford SL, Sutton K, Lou Y, Zhang Z, Tenorio A, Trezza C, Patel P, Spreen W. Effect of Rifampin on the Single-Dose Pharmacokinetics of Oral Cabotegravir in Healthy Subjects. Antimicrob Agents Chemother. 2017 Sep 22;61(10):e00487-17. doi: 10.1128/AAC.00487-17. Print 2017 Oct.

    PubMed 28739783

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing CAB and RIF in people with Infection, Human Immunodeficiency Virus, run by ViiV Healthcare 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 12 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 6 Jan 2016. 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?

Plasma CAB maximum observed concentration after single dose administration (Cmax) (time frame: Days 1, 2, 3, 4, 6, 8, 21, 22, 23, 24, 26, and 28). 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?

On the ClinicalTrials.gov record for NCT02411435, which also lists 1 linked publication.

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 6 Jan 2016.

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