Study to Evaluate the Safety Tolerability and Acceptability of Long Acting Injections of the Human Immunodeficiency Virus (HIV) Integrase Inhibitor, GSK1265744, in HIV Uninfected Men (ECLAIR)

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
GlaxoSmithKline
Information provided by (Responsible Party):
ViiV Healthcare
ClinicalTrials.gov Identifier:
NCT02076178
First received: February 27, 2014
Last updated: August 7, 2014
Last verified: August 2014

February 27, 2014
August 7, 2014
March 2014
May 2015   (final data collection date for primary outcome measure)
  • Safety and Tolerability as assessed by adverse events [ Time Frame: Up to Week 41 (Final visit) ] [ Designated as safety issue: No ]
    To evaluate the safety and tolerability of the injectable agent, 744 LA (800 mg dose administered at three time points at 12 week intervals) through Week 41 in HIV-uninfected men as assessed by adverse events
  • Safety and Tolerability as assessed by concurrent medication required [ Time Frame: Up to Week 41 (Final visit) ] [ Designated as safety issue: No ]
    To evaluate the safety and tolerability of the injectable agent, 744 LA (800 mg dose administered at three time points at 12 week intervals) through Week 41 in HIV-uninfected men as assessed by concurrent medication required
  • Safety and Tolerability as assessed by clinical laboratory tests [ Time Frame: Up to Week 41 ] [ Designated as safety issue: No ]
    To evaluate the safety and tolerability of the injectable agent, 744 LA (800 mg dose administered at three time points at 12 week intervals) through Week 41 in HIV-uninfected men as assessed by clinical laboratory tests (Hematology/Chemistry testing and Urinalysis)
  • Safety and Tolerability as assessed by Electrocardiogram (ECG) [ Time Frame: Up to Week 41 ] [ Designated as safety issue: No ]
    To evaluate the safety and tolerability of the injectable agent, 744 LA (800 mg dose administered at three time points at 12 week intervals) through Week 41 in HIV-uninfected men as assessed by ECG
  • Safety and Tolerability as assessed by vital signs assessments [ Time Frame: Up to Week 41 ] [ Designated as safety issue: No ]
    To evaluate the safety and tolerability of the injectable agent, 744 LA (800 mg dose administered at three time points at 12 week intervals) through Week 41 in HIV-uninfected men as assessed by vital signs assessments
  • Safety and Tolerability as assessed by injection site reactions (ISRs) [ Time Frame: Up to Week 41 (Final visit) ] [ Designated as safety issue: No ]
    To evaluate the safety and tolerability of the injectable agent, 744 LA (800 mg dose administered at three time points at 12 week intervals) through Week 41 in HIV-uninfected men as assessed by and injection site reactions (ISRs)
Same as current
Complete list of historical versions of study NCT02076178 on ClinicalTrials.gov Archive Site
  • Plasma pharmacokinetic profile for 744 [ Time Frame: Up to Week 41 ] [ Designated as safety issue: No ]
    The following pharmacokinetic parameters were evaluated following each IM injection of 744 LA through 41 weeks. For each 12-week dosing interval, parameters include: Individual plasma PK parameters for each injection interval will be determined, including: area under the plasma concentration time curve over the dosing interval (AUC(0-tau)), maximum observed concentration (Cmax), time to maximum observed concentration (tmax), concentration at the end of the dosing interval (Ctau), and apparent terminal phase half-life for LA administration (t½) and lambda z as a measure of absorption rate constant (lambda z) if data allow
  • 744 PK parameters as assessed by patient demographics (age, race, weight, BMI, and ethnicity) [ Time Frame: Up to Week 41 ] [ Designated as safety issue: No ]
    The following pharmacokinetic parameters following each IM injection of 744 LA through 41 weeks. AUC(0-tau), Ctau, Cmax, t1/2, and lambda z) by age, race, weight, BMI and ethnicity
  • Safety and tolerability of oral 744 [ Time Frame: Up to Week 4 ] [ Designated as safety issue: No ]
    To evaluate the safety and tolerability of oral 744 in HIV-uninfected men as assessed by adverse events, clinical laboratory tests (Hematology/Chemistry testing and Urinalysis) and concurrent medication required
  • Acceptability of 744 LA injections [ Time Frame: Week 5 to Week 41 ] [ Designated as safety issue: No ]
    Acceptability of 744 LA injections was assessed by incidence and severity of ISRs and ISR symptom score
  • Statistical evaluation for concentration-effect relationships for various safety parameters [ Time Frame: Up to Week 81 ] [ Designated as safety issue: No ]
    Pearson's correlations between PK parameters and safety parameters (occurrence of AEs, maximum intensity of AE per subject, and clinical laboratory parameters of special interest) may be presented. Logistic regression may be used to examine correlation between PK parameters and presence or absence of AEs of special interest from selected system organ class
Same as current
Not Provided
Not Provided
 
Study to Evaluate the Safety Tolerability and Acceptability of Long Acting Injections of the Human Immunodeficiency Virus (HIV) Integrase Inhibitor, GSK1265744, in HIV Uninfected Men (ECLAIR)
A Phase IIa Study to Evaluate the Safety, Tolerability and Acceptability of Long Acting Injections of the HIV Integrase Inhibitor, GSK1265744, in HIV Uninfected Men (ECLAIR)

This study is a Phase IIa, randomized, multi-site, two-arm, double-blinded study to evaluate the safety, tolerability, and acceptability of GSK1265744 long acting injectable formulation (744 LA) in adult male subjects. To evaluate the safety and tolerability of the injectable agent, 744 LA (800 milligrams (mg) dose administered at three time points at 12 week intervals) through Week 41 in HIV-uninfected men. Eligible participants will be randomized in a 5:1 ratio to receive 744 LA or matching placebo. Participants will receive daily oral 744 (30 mg tablets) or matching placebo for 4 weeks during the Oral Phase of the study, followed by a one week washout period. Following safety lab assessments from the Oral Phase, participants will enter the Injection Phase and receive Intramuscular (IM) injections of 744 LA or placebo at three time points at 12 week intervals. IM injections will consist of 800 mg of 744 or a matching control

Not Provided
Interventional
Phase 2
Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Infection, Human Immunodeficiency Virus
  • Drug: 744 Tablet
    White to almost white oval shaped film coated 30 mg tablets for oral administration
  • Drug: 744 LA Injection
    Sterile white to slightly coloured suspension containing 200 mg/mL of 744 as free acid for administration by intramuscular (IM) injection
  • Drug: Placebo Tablet
    Microcrystalline cellulose, Opadry film-coating, white OY-S-28876
  • Drug: Placebo Injection
    Sterile saline 0.9% Sodium Chloride Injection
  • Experimental: Arm 1
    Participants will receive daily oral 744 (30 mg tablets) for 4 weeks, followed by a one week washout period followed by intra-muscular (IM) injections of 800 mg of 744 LA at three time points at 12 week intervals as: Week 5, Week 17, and Week 29
    Interventions:
    • Drug: 744 Tablet
    • Drug: 744 LA Injection
  • Experimental: Arm 2
    Participants will receive daily oral matching placebo for 4 weeks, followed by a one week washout period followed by intra-muscular (IM) injections of saline at three time points at 12 week intervals as: Week 5, Week 17, and Week 29
    Interventions:
    • Drug: Placebo Tablet
    • Drug: Placebo Injection
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
120
March 2016
May 2015   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Non-reactive HIV test at screening or enrollment.
  • Males 18 to 65 years old at the time of signing the informed consent.
  • At risk of acquiring HIV, defined as having at least one casual sex partner in the past 24 months.
  • Healthy as determined by a responsible and experienced physician, based on a medical evaluation including medical history, physical examination, laboratory tests and cardiac monitoring at the time of screening.
  • If participating in sexual activity with a female of child-bearing potential, men must agree to use condoms. Subjects who are sexual partners of females with child bearing potential must also agree to practice an acceptable method of contraception for the duration of the study, such as double barrier (male condom/spermicide, male condom/diaphragm) or female partner use of hormonal contraception, intrauterine device (IUD) or other method with published data showing that the lowest expected failure rate for that is less than 1% per year. All subjects participating in the study must be counseled on safer sexual practices including the use of effective barrier methods to minimize risk of HIV transmission.
  • Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form.
  • Willing to undergo all required study procedures

Exclusion Criteria:

  • One or more reactive HIV test results at screening or enrollment, even if HIV infection is not confirmed. Negative HIV Ribonucleic acid (RNA) must also be documented at screening.
  • Assessed by the Investigator of Record or designee as being at "high risk" for HIV infection. This may include one or more of the following:

The negative partner in an HIV serodiscordant couple Men who exchange sex for goods or money Men who have engaged in unprotected receptive anal intercourse within the past 6 months Men who have had greater than 3 sexual partners within the past 3 months Men who have had a sexually transmitted disease within the past 6 months Any other behavior assessed by the investigator as "high risk"

  • Co-enrollment in any other HIV interventional research study (provided by self-report or other available documentation) or prior enrollment and receipt of the active arm (i.e., NOT a placebo) of a HIV vaccine trial (provided by available documentation).
  • Use of antiretroviral (ARV) therapy (e.g., for Post exposure prophylaxis (PEP) or Pre exposure prophylaxis (PrEP) in the past 30 days, five half-lives, or twice the duration of the biological effect of the applied treatment (whichever is longer) prior to study enrollment.
  • 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 drug or alcohol consumption that in the opinion of the Principal Investigator will interfere with study participation.
  • 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.
  • Any of the following laboratory values during the screening period. Positive Hepatitis C antibody result Positive Hepatitis B surface antigen (HBsAg) Hemoglobin less than 11 gram (g)/deci liter (dL) Absolute neutrophil count less than 750 cells/mm^3 Platelet count less than or equal to 100,000/mm^3 Presence of a coagulopathy as defined by an INR greater than 1.5 or a PTT greater than 45sec Calculated creatinine clearance less than 70 mL/minute using the Cockcroft-Gault equation A single repeat test is allowed during the Screening period to verify a result, with the exception of HIV tests.
  • Subjects with an alanine aminotransferase (ALT), alkaline phosphatase (ALP) or bilirubin greater than or equal to1.5xULN (isolated bilirubin greater than 1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin less than 35%).
  • History of the following cardiac diseases: myocardial infarction, congestive heart failure, documented hypertrophic cardiomyopathy, sustained ventricular tachycardia.
  • The subject's systolic blood pressure is outside the range of 90-160mmHg, or diastolic blood pressure is outside the range of 45-90mmHg or heart rate is outside the range of 45-100 beats per minute (bpm).
  • Exclusion criteria for screening (ECG (a single repeat is allowed for eligibility determination) for Male Subjects:

Heart rate (A heart rate from 100 to 110 bpm can be rechecked within 30 minutes to verify eligibility)-less than 45 and greater than 100 bpm.

QRS duration-greater than 120 msec. QTc interval (B or F)-greater than 450 msec. Evidence of previous myocardial infarction (does not include ST segment changes associated with repolarization).

Any conduction abnormality (including but not specific to left or right complete bundle branch block, AV block [2nd degree or higher], Wolf Parkinson White [WPW] syndrome).

Sinus Pauses greater than 3 seconds. Any significant arrhythmia which, in the opinion of the principal investigator and medical monitor, will interfere with the safety for the individual subject.

Non-sustained or sustained ventricular tachycardia (greater than or equal to 3 consecutive ventricular ectopic beats).

  • Ongoing intravenous drug use - episodic use or any use in the past 90 days is exclusionary (as assessed by the study investigator).
  • The subject has a tattoo or other dermatological condition overlying the gluteus region which may interfere with interpretation of ISRs.
  • Use of high dose aspirin or any other anticoagulant or antiplatelet medication that would interfere with the ability to receive intramuscular injections.
  • Active skin disease or disorder (i.e., infection, inflammation, dermatitis, eczema, drug rash, psoriasis, urticaria). Mild cases of localized acne or folliculitis or other mild skin condition may not be exclusionary at the discretion of the Investigator of Record or Medical Monitor).
Male
18 Years to 65 Years
Yes
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT02076178
201120
No
ViiV Healthcare
ViiV Healthcare
GlaxoSmithKline
Study Director: GSK Clinical Trials ViiV Healthcare
ViiV Healthcare
August 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP