None listed
Conditions
Brief summary
This is a first-in-human, Phase 1 study to evaluate the safety, tolerability, and pharmacokinetics of escalating, single and multiple oral doses of GS-1701 administered in healthy participants. This study will also evaluate the effect of food on the pharmacokinetics of GS-1701.
Interventions
The study will proceed in 2 parts (Parts A and B) of up to 7 cohorts, with dose selection and escalation governed within and between cohorts by the Safety Review Team (SRT)/dose-escalation team review of safety, tolerability, and any available pharmacokinetics (PK) data as well as by applicable stopping rules. Part B (Cohorts 5 to 7) may be initiated in parallel with the SAD cohorts if the dose is equal to or below the highest single dose for which available data from the SAD cohort(s) have been
The study will proceed in 2 parts (Parts A and B) of up to 7 cohorts, with dose selection and escalation governed within and between cohorts by the Safety Review Team (SRT)/dose-escalation team review of safety, tolerability, and any available pharmacokinetics (PK) data as well as by applicable stopping rules. Part B (Cohorts 5 to 7) may be initiated in parallel with the SAD cohorts if the dose is equal to or below the highest single dose for which available data from the SAD cohort(s) have been reviewed and no dose-limiting toxicity (DLT) or prespecified stopping criteria have been identified. Study drug adherence to be monitored by the Investigator. Part A (Single Ascending Doses [SAD] and SAD/Food Effect [FE]) - Cohort 1 - Day 1: single dose of 100 mg of GS-1701 or placebo-to-match (PTM) in the morning, orally, fasted state - Cohort 2 (Adaptive) - Day 1: single dose of up to 300 mg of GS-1701 or PTM in the morning, orally, fasted state - Cohort 3 (Adaptive, FE) – Day 1: single dose of up to 1000 mg of GS-1701 or PTM in the morning, orally, fasted state; Day 7: single dose of up to 1000 mg of GS-1701 or PTM in the morning, orally, fed (high-fat meal) state. - Cohort 4 (Adaptive) – Day 1: single dose of up to 3000 mg of GS-1701 or PTM in the morning, orally, fasted state Part B (Multiple Ascending Doses [MAD]) - Cohort 5 (Adaptive) - Days 1-14: up to 1000 mg once daily of GS-1701 or PTM in the morning, orally, fasted state, or up to 500 mg twice daily of GS-1701 or PTM in the morning and in the evening, orally, both fasted state - Cohort 6 (Adaptive) - Days 1-14: up to 2000 mg once daily of GS-1701 or PTM in the morning, orally, fasted state, or up to 1000 mg twice daily of GS-1701 or PTM in the morning and in the evening, orally, both fasted state - Cohort 7 (Adaptive) - Days 1-14: up to 3000 mg once daily of GS-1701 or PTM in the morning, orally, fasted state, or up to 1500 mg twice daily of GS-1701 or PTM in the morning and in the evening, orally, fasted state
Sponsors
Gilead Sciences Inc
Study design
Allocation
Randomised controlled trial
Intervention model
Other
Primary purpose
Treatment
Eligibility
Sex/Gender
All
Age
18 Years to 45 Years
Healthy volunteers
Yes
Inclusion criteria
- Participants assigned male or female at birth, aged 18 years through 45 years inclusive, and able to comply with treatment and follow-up. - Be a nonsmoker. The use of nicotine or nicotine-containing products must be discontinued greater than or equal to 90 days prior to the first dose of study drug. - Must, in the opinion of the investigator, be in good health based on medical history and physical examination, including vital signs. - Have a calculated body mass index (BMI) of greater than or equal to 19.0 and less than or equal to 30.0 kg/m2 at screening and at admission. - Negative serum pregnancy test at screening and at admission. - Have an estimated glomerular filtration rate (eGFR) calculated using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation of greater than or equal to 90 mL/minute/1.73m2 at screening and at admission.
Exclusion criteria
- Breastfeeding or lactating participant - Have a history of any of the following: - Significant serious skin disease, such as but not limited to rash, eczema, psoriasis, or urticaria. - Significant drug sensitivity or drug allergy (such as but not limited to anaphylaxis or drug-induced liver injury). - Known hypersensitivity to the study drugs, their metabolites, or to formulation excipients for all cohorts. - Significant cardiac disease (including history of myocardial infarction based on ECG and/or clinical history, any history of ventricular tachycardia, congestive heart failure, or dilated cardiomyopathy with left ventricular ejection fraction less than or equal to 40%) or a family history of long QT syndrome, or unexplained death in an otherwise healthy individual between the ages of 1 and 30 years. - Syncope, palpitations, or unexplained dizziness. - Implanted defibrillator or pacemaker. - Liver disease, including Gilbert syndrome. - Severe peptic ulcer disease, gastroesophageal reflux disease, or other gastric acid hypersecretory conditions requiring prolonged (greater than or equal to 6 months) medical treatment. - Medical or surgical treatment that permanently altered gastric absorption (eg, gastric or intestinal surgery). A history of cholecystectomy is not exclusionary. - Have any serious or active medical or psychiatric illness (including depression) that, in the opinion of the investigator, would interfere with participant treatment, assessment, or compliance with the protocol. This would include renal, cardiac, hematological, hepatic, pulmonary (including chronic asthma), endocrine (including diabetes), central nervous, gastrointestinal (including an ulcer), vascular, metabolic (thyroid disorders, adrenal disease), immunodeficiency disorders, active infection, or malignancy that are clinically significant or requiring treatment. - Have a hemoglobin value less than 11.5 g/dL for females or less than 13.0 g/dL for males at screening. - Have a reticulocyte count less than 20 x 10^9/L at screening.
Outcome results
None listed