A Phase 1 Study of Novel GS-9973 Tablet Formulations to Evaluate the Effect of Acid Reducing Agents, Relative Bioavailability, and Food Effect on GS-9973 Pharmacokinetics

A Phase 1, Open-Label, Adaptive Study of Novel GS-9973 Tablet Formulations to Evaluate the Effect of Acid Reducing Agents, Relative Bioavailability, and Food Effect on GS-9973 Pharmacokinetics

This is a Phase 1, Open-Label, Adaptive Study of Novel GS-9973 Tablet Formulations to Evaluate the Effect of Acid Reducing Agents, Relative Bioavailability, and Food Effect on GS-9973 Pharmacokinetics.

Study Overview

• Status: Completed
• Conditions: Chronic Lymphocytic Leukemia
• Intervention / Treatment: Drug: Treatment A; Drug: Treatment B; Drug: Treatment G; Drug: Treatment I; Drug: Treatment C; Drug: Treatment H; Drug: Treatment J; Drug: Treatment D; Drug: Treatment E; Drug: Treatment F

• Study Type: Interventional
• Enrollment (Actual): 56
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Florida
    • Daytona Beach, Florida, United States, 32117
      • Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Have the ability to understand and sign a written informed consent form, which must be obtained prior to initiation of study procedures
• Must have a body mass index (BMI) range of approximately 19 to 30 kg/m2
• Must have a minimum weight of 45 kg

• Females of childbearing potential must have negative serum pregnancy tests at screening and baseline and must practice at least 1 reliable method of contraception as defined by the protocol

  • Female subjects who utilize hormonal contraceptive as 1 of their birth control methods must have used the same method for at least 3 months prior to study dosing
• Male subjects must agree to use condoms during heterosexual intercourse and avoid sperm donation from Day -1 until 90 days following the last dose of study medication
• Must refrain from blood donation throughout the study period
• Must, in the opinion of the Investigator, be in good general
• Must be a non- or light smoker, eg, less than 10 cigarettes per day

Exclusion Criteria:

• Pregnant or lactating subjects
• Use of prescribed or over-the-counter medications that affect gastric pH
• History of severe peptic ulcer disease, GERD, or other diseases requiring prolonged(>6 weeks) medication or surgical therapy to modify gastric pH
• Have a history of clinically significant cardiac abnormalities or presence of clinically significant abnormality on 12-lead ECG.
• Have a history of any cancer requiring systemic chemotherapy or radiation
• Have a history of bleeding disorders
• Have a history of liver disorders
• Current acute infection or history of acute infection within 7 days
• Have a recent history of alcohol or illicit drug abuse and/or have a positive test for selected drugs of abuse
• Have a positive hepatitis screen or positive Human Immunodeficiency Virus antibody test
• Have participated in another clinical trial within 28 days
• Have received transfusion of blood or plasma products within 6 months
• Have donated > 500 mL blood within 56 days
• Are unable or unwilling to comply with study restrictions, return for follow-up appointments, or other considerations, which in the opinion of the Investigator, would make the candidate unsuitable for study participation
• Current or historical medical condition that is deemed to be of medical significance by the Investigator
• Have used prescription medications, over the counter products, herbal remedies and nutritional supplements within 7 days

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Sequence 1	Drug: Treatment A; 1600 mg GS-9973 (Formulation 1); Drug: Treatment B; 1600 mg GS-9973 (Formulation 1) plus 20 mg omeprazole; Drug: Treatment G; 1600 mg GS-9973 (Reference formulation); Drug: Treatment I; An alternate dose of the chosen formulation from Part A up to 1200 mg administered twice-daily
Experimental: Sequence 2	Drug: Treatment A; 1600 mg GS-9973 (Formulation 1); Drug: Treatment C; 1600 mg GS-9973 (Formulation 1) plus 40 mg famotidine; Drug: Treatment H; 1600 mg GS-9973 (Formulation 1 or Formulation 2, based on results from Part A); Drug: Treatment J; An alternate dose of the chosen formulation from Part A up to 1200 mg administered twice-daily
Experimental: Sequence 3	Drug: Treatment G; 1600 mg GS-9973 (Reference formulation); Drug: Treatment I; An alternate dose of the chosen formulation from Part A up to 1200 mg administered twice-daily; Drug: Treatment D; 1600 mg GS-9973 (Formulation 2); Drug: Treatment E; 1600 mg GS-9973 (Formulation 2) plus 20 mg omeprazole
Experimental: Sequence 4	Drug: Treatment H; 1600 mg GS-9973 (Formulation 1 or Formulation 2, based on results from Part A); Drug: Treatment J; An alternate dose of the chosen formulation from Part A up to 1200 mg administered twice-daily; Drug: Treatment D; 1600 mg GS-9973 (Formulation 2); Drug: Treatment F; 1600 mg GS-9973 (Formulation 2) plus 40 mg famotidine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetic parameters for GS-9973	The primary outcome measure is the pharmacokinetic (PK) parameters for GS-9973 including AUC and Cmax.	Up to 3 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Secondary pharmacokinetic parameters for GS-9973	A secondary outcome measure is the pharmacokinetic parameters for GS-9973 including Ctau and AUClast.	Up to 3 months
Incidence of Adverse Events	A secondary outcome measure is the safety and tolerability of GS-9973 which will be evaluated by the incidence of AEs including assessment of clinical laboratory test findings, physical examinations, 12-lead ECG abnormalities, and vital signs measurements.	Up to 3 months
Blood PD parameters for GS-9973	A secondary outcome measure is the blood pharmacodynamic parameters.	Up to 3 months

Collaborators and Investigators

• Sponsor: Gilead Sciences
• Investigators: Study Director: Michael Hawkins, MD, Gilead Sciences

Study record dates

Study Major Dates

• Study Start: May 1, 2013
• Primary Completion (Actual): August 1, 2013
• Study Completion (Actual): October 1, 2013

Study Registration Dates

• First Submitted: April 24, 2013
• First Submitted That Met QC Criteria: April 24, 2013
• First Posted (Estimate): April 26, 2013

Study Record Updates

• Last Update Posted (Estimate): February 7, 2014
• Last Update Submitted That Met QC Criteria: February 5, 2014
• Last Verified: February 1, 2014

More Information

Terms related to this study

• Keywords: CLL; Chronic Lymphocytic Leukemia
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Leukemia; Leukemia, B-Cell; Leukemia, Lymphocytic, Chronic, B-Cell; Leukemia, Lymphoid
• Other Study ID Numbers: GS-US-339-0111