Study to Compare the Safety and Anti-HIV Effect of GSK1265744 Versus Placebo in HIV-1 Infected Adults (ITZ112929)

NCT00920426 | Completed Phase 2 Results

• 1 other identifier: 112929
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 4

Brief Summary

The purpose of this randomized, double-blinded study is to test the safety of GSK1265744 and how well it works on reducing the amount of HIV in the blood. It will also look at how people react to and how a human body uses GSK1265744. This study will compare the effects of GSK1265744 and placebo. The study will consist of 1 or 2 parts to look at doses of GSK1265744. About 8 people will take part in Part 1 of the study receiving dose A. If additional dosing information is needed after Part 1, about 6 people will take part in Part 2 of the study receiving dose B.

Conditions

Infection, Human Immunodeficiency Virus

Keywords

HIV; naive; Phase II; integrase inhibitor; GSK1265744; newly diagnosed; pharmacokinetics; AIDS; integrase; HIV Infections; Treatment naive

Outcome Measures

Primary Outcomes (25)

• Change From Baseline in Plasma Human Immunodeficiency Virus (HIV-1) Ribonucleic Acid (RNA) to Day 11

  Plasma for quantitative HIV-1 RNA was collected on Day 1, 2, 3, 4, 7, 8, 9, 10 and 11. On Days 1, 10 and 11, two samples for HIV-1 RNA was collected between 5-20 minutes apart to reduce sample variability. An HIV-1 RNA PCR assay with a lower limit of detection (LLOD) of 50 copies/milliliter (mL) (ultrasensitive assay) was used for post-baseline assessments. An HIV-1 RNA PCR assay with a LLOD of 400 copies/mL (standard assay) was used for screening and Baseline assessments and included a re-test with and ultrasensitive assay for all Baseline values below the LLOD. Baseline was defined at Day 1. The change from Baseline was calculated by subtracting the Baseline values from the individual post-randomization values.

  Baseline (Day 1) and Day 11

• GSK1265744 Pharmacokinetic (PK) Parameters Following Dose Administration on Day 1: Area Under the Concentration-time Curve From Time Zero (Pre-dose) to Last Time of Quantifiable Concentration Within a Participant Across All Treatments(AUC[0-24])

  Blood samples for PK analysis of AUC(0-24) of GSK1265744 was collected on Day 1 (Pre-dose \[within 15 minutes prior to dosing\] and at 0.5, 1, 1.5, 2, 3, 4, 6, and 8hours post-dose). Samples were collected at nominal times relative to the proposed time of GSK1265744 dosing. The actual date and time of each blood sample collection was recorded. AUC was determined using the linear trapezoidal rule for increasing concentrations and the logarithmic trapezoidal rule for decreasing concentrations.

  Day 1 (Pre-dose [within 15 minutes prior to dosing] and at 0.5, 1, 1.5, 2, 3, 4, 6, and 8hours post-dose)

• GSK1265744 PK Parameters Following Dose Administration on Day 1: Concentration at 24 Hours Post Dose (C24)

  Blood samples for PK analysis of C24 of GSK1265744 was collected on Day 1 (Pre-dose \[within 15 minutes prior to dosing\] and at 0.5, 1, 1.5, 2, 3, 4, 6, and 8hours post-dose). Samples were collected at nominal times relative to the proposed time of GSK1265744 dosing. The actual date and time of each blood sample collection was recorded.

  Day 1 (Pre-dose [within 15 minutes prior to dosing] and at 0.5, 1, 1.5, 2, 3, 4, 6, and 8hours post-dose)

• GSK1265744 PK Parameters Following Dose Administration on Day 10: Area Under the Concentration-time Curve Over the Dosing Interval (AUC[0-tau])

  Blood samples for PK analysis of C24 of GSK1265744 was collected on Day 10 (Pre-dose \[within 15 minutes prior to dosing\] and at 0.5, 1, 1.5, 2, 3, 4, 6, and 8hours post-dose). Samples were collected at nominal times relative to the proposed time of GSK1265744 dosing. The actual date and time of each blood sample collection was recorded. AUC was determined using the linear trapezoidal rule for increasing concentrations and the logarithmic trapezoidal rule for decreasing concentrations.

  Day 10 (Pre-dose [within 15 minutes prior to dosing] and at 0.5, 1, 1.5, 2, 3, 4, 6, and 8hours post-dose)

• GSK1265744 PK Parameters Following Dose Administration on Day 10: Predose Concentration (C0), Concentration at End of Dosing Interval (Ctau), Minimum Observed Concentration During One Dosing Interval (Cmin)

  Blood samples for PK analysis of C0, Ctau and Cmin of GSK1265744 was collected on Day 10 (Pre-dose \[within 15 minutes prior to dosing\] and at 0.5, 1, 1.5, 2, 3, 4, 6, and 8hours post-dose). Samples were collected at nominal times relative to the proposed time of GSK1265744 dosing. The actual date and time of each blood sample collection was recorded.

  Day 10 (Pre-dose [within 15 minutes prior to dosing] and at 0.5, 1, 1.5, 2, 3, 4, 6, and 8hours post-dose)

• GSK1265744 PK Parameters Following Dose Administration on Day 1 and Day 10: Maximum Observed Concentration (Cmax)

  Blood samples for PK analysis of Cmax of GSK1265744 was collected at pre-dose (within 15 minutes prior to dosing) and at 0.5, 1, 1.5, 2, 3, 4, 6, and 8hours post-dose on Days 1 and 10. Samples were collected at nominal times relative to the proposed time of GSK1265744 dosing. The actual date and time of each blood sample collection was recorded.

  Pre-dose (within 15 minutes prior to dosing) and at 0.5, 1, 1.5, 2, 3, 4, 6, and 8hours post-dose on Days 1 and 10

• GSK1265744 PK Parameters Following Dose Administration on Day 1 and Day 10: Time to Cmax (Tmax)

  Blood samples for PK analysis of tmax of GSK1265744 was collected at pre-dose (within 15 minutes prior to dosing) and at 0.5, 1, 1.5, 2, 3, 4, 6, and 8hours post-dose on Days 1 and 10. Samples were collected at nominal times relative to the proposed time of GSK1265744 dosing. The actual date and time of each blood sample collection was recorded.

  Pre-dose (within 15 minutes prior to dosing) and at 0.5, 1, 1.5, 2, 3, 4, 6, and 8hours post-dose on Days 1 and 10

• GSK1265744 PK Parameters Following Dose Administration on Day 1 and Day 10: Terminal Half-life (t1/2) and Absorption Lag Time (Tlag)

  PK sampling was planned to be collected up to 24 hours only on Day 1 and Day 10. The data for this outcome measure was however not collected.

  Day 1 and Day 10

• GSK1265744 PK Parameters Following Last Repeat Administration on Day 10: Apparent Clearance Following Oral Dosing (CL/F)

  Blood samples for PK analysis of CL/F of GSK1265744 was collected on Day 10 (Pre-dose \[within 15 minutes prior to dosing\] and at 0.5, 1, 1.5, 2, 3, 4, 6, and 8hours post-dose). Samples were collected at nominal times relative to the proposed time of GSK1265744 dosing. The actual date and time of each blood sample collection was recorded.

  Day 10 (Pre-dose [within 15 minutes prior to dosing] and at 0.5, 1, 1.5, 2, 3, 4, 6, and 8hours post-dose)

• Number of Participants With Incidence of Adverse Events (AEs) and Serious Adverse Events (SAEs)

  An AE is any untoward medical occurrence in a participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. An SAE is any untoward medical occurrence that, at any dose results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, or is a congenital anomaly/birth defect, medically significant or is associated with liver injury and impaired liver function.

  Day 1 to Day 11

• Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils (ANC- Absolute Neutrophil Count), White Blood Cell Count

  Blood samples for assessment of hematology parameters of basophils, eosinophils, lymphocytes, monocytes, total neutrophils (ANC- absolute neutrophil count) and white blood cell count was collected at Baseline, Day 3, 7 and 10. Baseline was defined at Day 1. The change from Baseline was calculated by subtracting the Baseline values from the individual post-randomization values.

  Baseline (Day 1) and Day 3, 7, 10

• Change From Baseline in Hematology Parameters: Hemoglobin

  Blood samples for assessment of hematology parameter of hemoglobin was collected at Baseline, Day 3, 7 and 10. Baseline was defined at Day 1. The change from Baseline was calculated by subtracting the Baseline values from the individual post-randomization values.

  Baseline (Day 1) and Day 3, 7, 10

• Change From Baseline in Hematology Parameters: Mean Corpuscle Hemoglobin

  Blood samples for assessment of hematology parameter of mean corpuscle hemoglobin was collected at Baseline, Day 3, 7 and 10. Baseline was defined at Day 1. The change from Baseline was calculated by subtracting the Baseline values from the individual post-randomization values.

  Baseline (Day 1) and Day 3, 7, 10

• Change From Baseline in Hematology Parameters: Mean Corpuscle Volume

  Blood samples for assessment of hematology parameter of mean corpuscle volume was collected at Baseline, Day 3, 7 and 10. Baseline was defined at Day 1. The change from Baseline was calculated by subtracting the Baseline values from the individual post-randomization values.

  Baseline (Day 1) and Day 3, 7, 10

• Change From Baseline in Hematology Parameters: Platelet Count

  Blood samples for assessment of hematology parameter of platelet count was collected at Baseline, Day 3, 7 and 10. Baseline was defined at Day 1. The change from Baseline was calculated by subtracting the Baseline values from the individual post-randomization values.

  Baseline (Day 1) and Day 3, 7, 10

• Change From Baseline in Hematology Parameters: Red Blood Cell Count

  Blood samples for assessment of hematology parameter of red blood cell count was collected at Baseline, Day 3, 7 and 10. Baseline was defined at Day 1. The change from Baseline was calculated by subtracting the Baseline values from the individual post-randomization values.

  Baseline (Day 1) and Day 3, 7, 10

• Change From Baseline in Hematology Parameters: Reticulocytes

  Blood samples for assessment of hematology parameter of reticulocytes was collected at Baseline, Day 3, 7 and 10. Baseline was defined at Day 1. The change from Baseline was calculated by subtracting the Baseline values from the individual post-randomization values.

  Baseline (Day 1) and Day 3, 7, 10

• Change From Baseline in Clinical Chemistry Data: Albumin, Total Protein

  Blood samples for assessment of clinical chemistry parameters of albumin and total protein was collected at Baseline, Day 3, 7 and 10. Baseline was defined at Day 1. The change from Baseline was calculated by subtracting the Baseline values from the individual post-randomization values.

  Baseline (Day 1) and Day 3, 7, 10

• Change From Baseline in Clinical Chemistry Data: Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase, Creatine Kinase, Lipase

  Blood samples for assessment of clinical chemistry parameters of alkaline phosphatase, alanine amino transferase, aspartate amino transferase, creatine kinase and lipase was collected at Baseline, Day 3, 7 and 10. Baseline was defined at Day 1. The change from Baseline was calculated by subtracting the Baseline values from the individual post-randomization values.

  Baseline (Day 1) and Day 3, 7, 10

• Change From Baseline in Direct Bilirubin, Total Bilirubin, Calcium, Cholesterol, Creatinine, Glucose, High Density Lipoprotein (HDL) Cholesterol Direct, Low Density Lipoprotein (LDL) Cholesterol Calculation, Triglycerides, Urea/Blood Urea Nitrogen

  Blood samples for assessment of clinical chemistry parameters of direct bilirubin, total bilirubin, calcium, cholesterol, creatinine, glucose, HDL cholesterol direct, LDL cholesterol calculation, triglycerides,Urea/BUN was collected at Baseline, Day 3, 7 and 10. Baseline was defined at Day 1. The change from Baseline was calculated by subtracting the Baseline values from the individual post-randomization values.

  Baseline (Day 1) and Day 3, 7, 10

• Change From Baseline in Clinical Chemistry Data: Chloride, Carbon Dioxide Content/Bicarbonate, Magnesium, Sodium, Potassium

  Blood samples for assessment of clinical chemistry parameters of chloride, carbon dioxide content/bicarbonate, magnesium, sodium and potassium was collected at Baseline, Day 3, 7 and 10. Baseline was defined at Day 1. The change from Baseline was calculated by subtracting the Baseline values from the individual post-randomization values.

  Baseline (Day 1) and Day 3, 7, 10

• Number of Participants With Urinalysis Data

  Samples for urinalysis assessment was collected on Day 1, Day 3 and Day 10. Urinalysis parameters included urine bilirubin, urine occult blood, urine glucose, urine ketones, urine nitrite, urine pH, urine protein, urine specific gravity and urine leukocyte esterase test for detecting white blood cell.

  Day 1 to Day 10

• Change From Baseline in Vital Sign: Systolic and Diastolic Blood Pressure

  Systolic and diastolic blood pressure was measured at Baseline (Day 1 pre-dose), 2 hour post dose on Day 1, pre-dose on Day 4, 7, 10 and 2 hours post dose on Day 10. Baseline was defined at Day 1 pre-dose. The change from Baseline was calculated by subtracting the Baseline values from the individual post-randomization values.

  Baseline (Day 1, pre-dose) and Day 1 (2 hours post dose), 4, 7, 10

• Change From Baseline in Vital Sign: Heart Rate

  Heart rate was measured at Baseline (Day 1 pre-dose), 2 hour post dose on Day 1, pre-dose on Day 4, 7, 10 and 2 hours post dose on Day 10. Baseline was defined at Day 1 pre-dose. The change from Baseline was calculated by subtracting the Baseline values from the individual post-randomization values.

  Baseline (Day 1, pre-dose) and Day 1 (2 hours post dose), 4, 7, 10

• Change From Baseline in Electrocardiogram (ECG) Parameters

  All ECGs were obtained after a minimum 10 minute rest in a semi-supine position. The 12-lead ECGs were obtained at Baseline (Day 1 pre-dose), 2 hour post dose on Day 1, pre-dose on Day 4, 7, 10 and 2 hours post dose on Day 10 using an ECG machine that automatically calculated the heart rate and measured PR, QRS, QT, and Bazett's correction (QTcB) and Fridericia correction (QTcF) intervals. Baseline was defined at Day 1 pre-dose. The change from Baseline was calculated by subtracting the Baseline values from the individual post-randomization values.

  Baseline (Day 1, pre-dose) and Day 1 (2 hours post dose), 4, 7, 10

Secondary Outcomes (12)

• Change From Baseline in Plasma HIV-1 RNA

  Baseline (Day 1 pre-dose) and Day 1 (post dose), 2, 3, 4, 7, 8, 9, 10

• Change From Baseline in Plasma HIV-1 RNA to Nadir Over 11 Days

  Baseline (Day 1) and Day 11

• Plasma HIV-1 RNA Rate of Decline (Slope) Over 11 Days

  Up to Day 10

• Number of Participants With HIV-1 RNA<400 Copies/mL

  Up to Day 11

• Number of Participants With HIV-1 RNA<50 Copies/mL

  Up to Day 11

Study Arms (3)

GSK1265744 30 mg

EXPERIMENTAL

GSK1265744 30 mg

Drug: GSK1265744 30mg

Placebo

EXPERIMENTAL

Placebo to match GSK1265744

Drug: Placebo

GSK1265744 5 mg

EXPERIMENTAL

GSK1265744 5 mg

Drug: GSK1265744 5mg

Interventions

GSK1265744 30mg DRUG

GSK1265744 30 mg

GSK1265744 30 mg

Placebo DRUG

Placebo to match GSK1265744

Placebo

GSK1265744 5mg DRUG

GSK1265744 5mg

GSK1265744 5 mg

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female between 18 and 65 years of age inclusive, at the time of signing the informed consent.
• A female subject is eligible to participate if she is of non-childbearing potential, defined as:
• Pre-menopausal females with a documented bilateral oophorectomy, tubal ligation or hysterectomy; or
• Postmenopausal defined as 12 months of spontaneous amenorrhea. A follicle stimulating hormone level will be performed to confirm post-menopausal status. For this study, FSH levels \> 40 MlU/ml and estradiol \< 40 pg/ml (\<140 pmol/L) is confirmatory.
• Male subjects must agree to use one of the contraception methods listed in Section 8.1. This criterion must be followed from the time of the first dose of study medication until 14 days after the last dose of study medication.
• CD4+ cell count greater than or equal to 200 cells/mm3 and plasma HIV-1 RNA greater than or equal to 5000 copies/mL at Screening.
• No current antiretroviral therapy and have not received any in the 12 weeks prior to first dose.
• For subjects who have received antiretroviral treatment in the past, adequate treatment options to construct HAART therapy with at least 3 active antiretrovirals for Optimized Therapy, as selected by the Investigator.
• Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form.

You may not qualify if:

• A positive screening Hepatitis B surface antigen; positive screening hepatitis C virus (HCV) antibody and detectable HCV ribonucleic acid (RNA) on subsequent testing. If the hepatitis C antibody is positive but the HCV RNA is undetectable, the subject may be included in the study.
• AST and ALT \> 3ULN at Screening. A single repeat is allowed for eligibility determination.
• Inadequate renal function at Screening, defined as either a serum creatinine \>1.5 mg/dL or a calculated creatinine clearance (CrCl) ≤ 50 mL/min. A single repeat serum creatinine is allowed to determine eligibility.
• Any acute laboratory abnormality at screening which, in the opinion of the investigator, should preclude the subject's participation in the study of an investigational compound. Any grade 4 laboratory abnormality at screening, with the exception of CPK, will exclude a subject from study participation unless the investigator can provide a compelling explanation for the laboratory result(s) and has the assent of the sponsor. A single repeat is allowed for eligibility determination.
• A positive drug screen at screening and baseline. A minimum list of drugs that will be screened for include amphetamines, barbiturates, cocaine or PCP.
• History of regular alcohol consumption, defined as an average weekly intake of \>14 drinks for males or \>7 drinks for females, within 6 months of Screening.
• Note: One drink is equivalent to 12 g 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.
• Any condition (including alcohol or drug abuse) which, in the opinion of the investigator, could interfere with the subject's ability to comply with the dosing schedule and protocol evaluations or which might compromise the safety of the subject.
• Prior treatment with an integrase inhibitor (greater than or equal to 1 dose).
• Treatment with radiation therapy or cytotoxic chemotherapeutic agents within 30 days of study drug administration or anticipated need for such treatment within the study.
• Treatment with immunomodulating agents (such as systemic corticosteroids, interleukins, interferons) or any agent with known anti-HIV activity (such as hydroxyurea or foscarnet) within 30 days of study drug administration.
• Treatment with any vaccine within 30 days prior to receiving study medication.
• An active Center for Disease Control and Prevention (CDC) Category C disease, except cutaneous Kaposi's sarcoma not requiring systemic therapy during the trial.
• Pregnant females as determined by positive serum or urine hCG test at screening or prior to dosing.
• Lactating females.

Sponsors & Collaborators

• ViiV Healthcare: lead
• Shionogi: collaborator
• GlaxoSmithKline: collaborator

Study Sites (4)

GSK Investigational Site

Fort Lauderdale, Florida, 33308, United States

Location

GSK Investigational Site

Orlando, Florida, 32803, United States

Location

GSK Investigational Site

Vero Beach, Florida, 32960, United States

Location

GSK Investigational Site

Charlotte, North Carolina, 28209, United States

Location

MeSH Terms

Conditions

Infections; Acquired Immunodeficiency Syndrome; HIV Infections

Interventions

cabotegravir

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Slow Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Results Point of Contact

• Title: GSK Response Center
• Organization: ViiV Healthcare

866-435-7343

Study Officials

• GSK Clinical Trials

  ViiV Healthcare

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 12, 2009
• First Posted: June 15, 2009
• Study Start: June 9, 2009
• Primary Completion: August 13, 2009
• Study Completion: August 13, 2009
• Last Updated: December 6, 2017
• Results First Posted: December 6, 2017

Record last verified: 2017-09

Locations

US (4)