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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Chronic Lymphocytic Leukemia

Intervention / Treatment
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* Drug: Treatment A
* Drug: Treatment B
* Drug: Treatment C
* Drug: Treatment D
* Drug: Treatment E
* Drug: Treatment F
* Drug: Treatment G
* Drug: Treatment H
* Drug: Treatment I
* Drug: Treatment J


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

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

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Chronic Lymphocytic Leukemia, CLL