A Double-blind, Randomized, Placebo-controlled Phase 1/2 Study of the Safety, Pharmacokinetics, and Antiviral Activity of GS-9131 in Antiretroviral-Naive, HIV-1 Infected Subjects.

• Register: EUCTR
• Last refreshed on: 19 March 2012
• Main ID: EUCTR2008-002045-23-GB
• Date of registration: 28/05/2008
• Prospective Registration: Yes
• Primary sponsor: Gilead Sciences Incorporated
• Public title: A Double-blind, Randomized, Placebo-controlled Phase 1/2 Study of the Safety, Pharmacokinetics, and Antiviral Activity of GS-9131 in Antiretroviral-Naive, HIV-1 Infected Subjects.
• Scientific title: A Double-blind, Randomized, Placebo-controlled Phase 1/2 Study of the Safety, Pharmacokinetics, and Antiviral Activity of GS-9131 in Antiretroviral-Naive, HIV-1 Infected Subjects.
• Date of first enrolment: 18/07/2008
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2008-002045-23
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no

Countries of recruitment

United Kingdom

Key inclusion & exclusion criteria

Inclusion criteria:
Subjects must meet all of the inclusion criteria at screening to be eligible for participation in this study:

• Have the ability to understand and sign a written informed consent form, which must be obtained prior to initiation of study procedures.
• Must be between 18 and 65 years of age, inclusive.
• Weight = 50 kg
• Life expectancy = 1 year
• Must be antiretroviral treatment–naive (defined as = 14 days of therapy with any
antiretroviral drug, and not on therapy in the past 90 days prior to baseline)
• Plasma HIV-1 RNA levels of = 10,000 to = 100,000 copies/mL
• CD4+ cell count of = 200 cells/mm3
• Adequate renal function:
- Serum creatinine < 1.5 mg/dL [< 129 umol/L]
- Estimated glomerular filtration rate = 80 mL/min using the Cockcroft-Gault formula
{2202} based on serum creatinine and actual body weight as measured at the
screening evaluation, i.e.
Male: (140 – age in years) × (wt in kg) = Clcr (mL/min) /
72 × (serum creatinine in mg/dL)

Female: (140 – age in years) × (wt in kg) × 0.85 = Clcr (mL/min) /
72 × (serum creatinine in mg/dL)

• Adequate hepatic function:
- Hepatic transaminases (AST and ALT) = 2.5 × upper limit of normal (ULN)
- Total bilirubin = 1.5 mg/dL [= 26 umol/L]
• Adequate hematologic function (absolute neutrophil count = 1,000/mm3; platelets
= 50,000/mm3; hemoglobin = 8.0 g/dL)
• Serum amylase = 1.5 × ULN (subjects with serum amylase > 1.5 × ULN will remain
eligible if serum lipase is = 1.5 × ULN)
• Must be hepatitis B (HBV) surface antigen negative
• Must be hepatitis C (HCV) antibody negative
• Have either a normal 12-lead electrocardiogram (ECG) or one with abnormalities that are considered clinically insignificant by the investigator
• Must have a negative serum pregnancy test (females of childbearing potential only)
• Females of childbearing potential (i.e., no hysterectomy, bilateral oophorectomy, or
medically documented ovarian failure or less than 2 years postmenopausal) must agree to utilize highly effective contraception methods from screening visit and for 90 days following the last dose of study drugs; highly effective methods normally utilize two separate forms of contraception, one of which must be an effective barrier
contraceptive method
• Female subjects who utilize hormonal contraceptive as one of their birth control methods must have used the same method for at least three months prior to study dosing
• Female subjects who are postmenopausal for less than two years are required to have FSH = 40 mIU/mL. If the FSH is < 40 mIU/mL, the subject must agree to use highly effective method of birth control (as described above) to participate in the study
• Male subjects who are sexually active must be willing to use effective barrier
contraception (e.g., condom with spermicide) during heterosexual intercourse from
screening through completion of the study and continuing for at least 90 days from date of last dose of study drug
• Must, in the opinion of the investigator, be in good health based upon medical history, physical examination (including vital signs), and screening laboratory evaluations (hematology, chemistry, and urinalysis) must fall within the normal range of the laboratory’s reference ranges unless the results have been determined by the investigator to have no clinical significance
• Must be willing and able to comply with all study requirements
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults
Exclusion criteria:
Subjects who meet any of the following exclusion criteria are not to be enrolled in (or may be discontinued from) this study:

• Immunization within 30 days prior to baseline
• A new AIDS-defining condition diagnosed within the 30 days prior to baseline. (Refer to Appendix 5)
• Pregnant or lactating subjects
• Malignancy other than cutaneous Kaposi’s sarcoma (KS) or basal cell carcinoma.
Subjects with biopsy-confirmed cutaneous KS are eligible, but must not have received
any systemic therapy for KS within 30 days of baseline and are not anticipated to require systemic therapy during the study
• Active, serious infections (other than HIV-1 infection) requiring parenteral antibiotic or anti-fungal therapy within 30 days prior to baseline
• Have any serious or active medical or psychiatric illness which, in the opinion of the
investigator, would interfere with subject treatment, assessment, or compliance with the protocol. This would include renal, cardiac, hematological, hepatic, pulmonary (including chronic asthma), endocrine (e.g., diabetes), central nervous, astrointestinal (including an ulcer), vascular, metabolic (thyroid disorders, adrenal disease), immunodeficiency disorders, active infection, or malignancy that are clinically significant or requiring treatment
• Have previously participated in an investigational trial involving administration of any investigational compound within 30 days prior to the study dosing
• Current alcohol or substance abuse judged by the investigator to potentially interfere with subject compliance. Subjects receiving methadone maintenance therapy are not eligible to enroll in the study due to unknown potential for drug interaction
• Have history of significant drug sensitivity or drug allergy
• On-going therapy with any of the following:
- Any drug with antiretroviral activity except for the study drug
- Nephrotoxic agents
- aminoglycoside antibiotics
- IV amphotericin B
- cidofovir
- cisplatin
- foscarnet
- IV vancomycin
- oral and IV ganciclovir, or valganciclovir
- other agents with significant nephrotoxic potential
• Probenecid
• Systemic chemotherapeutic agents
• Systemic corticosteroids
• Immunosuppressant therapies
• Immunomodulating agents (i.e., Interleukin-2 [IL-2])
• Investigational agents (except upon approval by Gilead Sciences)

Administration of any of the above medications must be discontinued at least 30 days prior to the baseline visit and for the duration of the study period
• Have poor venous access and are unable to donate blood
• Are unable to comply with study requirements
• Believed, by the study investigator, to be inappropriate for study participation for any reason


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Antiretroviral treatment–naive subjects chronically infected with HIV-1
MedDRA version: 9.1 Level: LLT Classification code 10020192 Term: HIV-1

Intervention(s)

Product Name: GS-9131
Product Code: GS-9131
Pharmaceutical Form: Tablet
CAS Number: 912809-27-9
Current Sponsor code: GS-9131-01 (citrate salt)
Other descriptive name: GS-9131 (free base)
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 30-
Pharmaceutical form of the placebo: Tablet
Route of administration of the placebo: Oral use

Primary Outcome(s)

Primary end point(s): Maximum reduction from baseline in HIV-1 RNA (log10 copies/mL) on measurements taken between study Days 2 to 11.

Main Objective: To investigate the safety, tolerability, and antiviral activity of GS-9131 administered orally as ten consecutive once-daily doses in antiretroviral-naive subjects chronically infected with HIV-1.

Secondary Objective:

Secondary ID(s)

GS-US-180-0104