Double-Blind, Randomized, 2-Way Crossover Evaluation of the Impact of a Histamine-H2 Receptor Antagonist (H2RA) on the Pharmacokinetics of Telaglenastat Administered to Healthy Adult Subjects
Overview
- Phase
- Phase 1
- Intervention
- Telaglenastat
- Conditions
- Drug Interaction
- Sponsor
- Calithera Biosciences, Inc
- Enrollment
- 22
- Locations
- 1
- Primary Endpoint
- Area under the concentration-time curve from time = 0 to infinity (AUC0-inf)
- Status
- Completed
- Last Updated
- 5 years ago
Overview
Brief Summary
This study is designed to formally evaluate the impact of famotidine, an H2R antagonist, on the pharmacokinetics of telaglenastat.
This study will be conducted in up to 22 healthy volunteers, who meet all of the inclusion criteria and none of the exclusion criteria. The study is double-blinded, randomized 2-way crossover in design.
Subjects will receive four 200 mg tablets of telaglenastat either in the presence or absence of 20 mg famotidine (H2R-antagonist) with a 4-day wash-out period in between each regimen.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Healthy adult male or female, 18-55 years of age, inclusive, at screening.
- •Has not used nicotine-containing products (more than 5 cigarettes/equivalent per week) for at least 3 months prior the first dose and has negative urine cotinine tests at screening, Day 1 and Day
- •Body mass index (BMI) between 18.0 and 32.0 kg/m2, inclusively, at screening.
- •Medically healthy with no clinically significant medical history, physical examination, laboratory profiles, vital signs, or ECGs, as deemed by the Principal Investigator (PI).
- •For a female of childbearing potential: either be sexually inactive (abstinent - ie, not sexually active with a male partner) for 14 days prior to the first dose and through 14 days following the last dose of any study drug(s) or be using one of the following acceptable birth control methods:
- •Non-hormone releasing intrauterine device in place for at least 3 months prior to the first dose of any study drug with a physical barrier method (eg, condom, diaphragm) from the time of screening through the last dose of any study drug. A progesterone (progestin)-only contraceptive is allowable.
- •A physical barrier method (eg, condom, diaphragm) for at least 14 days prior to the first dose of any study drug and until the last dose of any study drug.
- •In addition, female subjects of childbearing potential will be advised to remain sexually inactive or to keep the same birth control method until the last dose of any study drug.
- •Females of non-childbearing potential as defined below do not require contraception.
- •Females of non-childbearing potential:
Exclusion Criteria
- •Subject is mentally or legally incapacitated or has significant emotional problems at the time of the screening visit or is expected to manifest significant emotional problems during the conduct of the study.
- •History or presence of clinically significant medical or psychiatric condition or disease in the opinion of the PI.
- •History of any illness that, in the opinion of the PI, might confound the results of the study or poses an additional risk to the subject by their participation in the study.
- •History or presence of alcoholism or drug abuse within the past 2 years prior to screening.
- •History or presence of hypersensitivity or idiosyncratic reaction to the study drugs or inactive ingredient(s).
- •History or presence of:
- •liver disease, pancreatic insufficiency or intestinal malabsorption;
- •neuropathy or muscle disorders;
- •asthma; childhood asthma that has resolved and has not required medical treatment for at least 5 years prior to study start is permitted;
- •fluid retention;
Arms & Interventions
Telaglenastat and Famotidine
Famotidine
Intervention: Telaglenastat
Telaglenastat and Famotidine
Famotidine
Intervention: Famotidine
Telaglenastat and Placebo for Famotidine
Placebo for famotidine
Intervention: Telaglenastat
Telaglenastat and Placebo for Famotidine
Placebo for famotidine
Intervention: Placebo for famotidine
Outcomes
Primary Outcomes
Area under the concentration-time curve from time = 0 to infinity (AUC0-inf)
Time Frame: Blood samples taken on Day 3 and Day 9 at 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 18, 24 hours post administration of the telaglenastat with and without famotidine.
To assess the effect of famotidine on the AUC0-inf of telaglenastat in healthy adult subjects
Area under the concentration-time curve from time = 0 to the last determination (AUClast)
Time Frame: Blood samples taken on Day 3 and Day 9 at 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 18, 24 hours post administration of the telaglenastat with and without famotidine.
To assess the effect of famotidine on the time to maximum plasma concentration (Tmax) of telaglenastat in healthy adult subjects.
Peak Plasma Concentration (Cmax)
Time Frame: Blood samples taken on Day 3 and Day 9 at 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 18, 24 hours post administration of the telaglenastat
To assess the effect of famotidine on the Cmax of telaglenastat in healthy adult subjects
Time to peak plasma concentration (Tmax)
Time Frame: Blood samples taken on Day 3 and Day 9 at 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 18, 24 hours post administration of the telaglenastat
To assess the effect of famotidine on the Tmax of telaglenastat in healthy adult subjects
Half-life
Time Frame: Blood samples taken on Day 3 and Day 9 at 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 18, 24 hours post administration of the telaglenastat with and without famotidine.
To assess the effect of famotidine on the half-life of telaglenastat in healthy adult subjects
Elimination rate
Time Frame: Blood samples taken on Day 3 and Day 9 at 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 18, 24 hours post administration of the telaglenastat with and without famotidine.
To assess the effect of famotidine on the elimination rate of telaglenastat in healthy adult subjects
Secondary Outcomes
- Serum bilirubin(Assessments will be performed prior to dosing with telaglenastat on Days 2 and 9 and 24 hours after dosing on Days 4 and 11.)
- Serum urea(Assessments will be performed prior to dosing with telaglenastat on Days 2 and 9 and 24 hours after dosing on Days 4 and 11.)
- Incidence of Treatment-Emergent Adverse Events(Safety will be assessed throughout the study, starting from Day 3, prior to receiving the first dose of telaglenastat through to Day 11 when the subjects are released from the clinical site.)
- Incidence of changes in body temperature(Body temperature will be assessed prior to dosing with telaglenastat on Days 2 and 9 and 24 hours after dosing on Days 4 and 11.)
- Incidence of changes in heart rate.(Heart rate will be assessed prior to dosing with telaglenastat on Days 2 and 9 and 24 hours after dosing on Days 4 and 11.)
- Hematocrit assessments(Assessments will be performed prior to dosing with telaglenastat on Days 2 and 9 and 24 hours after dosing on Days 4 and 11.)
- Leukocyte count assessments(Assessments will be performed prior to dosing with telaglenastat on Days 2 and 9 and 24 hours after dosing on Days 4 and 11.)
- Red blood cell count assessments(Assessments will be performed prior to dosing with telaglenastat on Days 2 and 9 and 24 hours after dosing on Days 4 and 11.)
- Platelet count assessments(Assessments will be performed prior to dosing with telaglenastat on Days 2 and 9 and 24 hours after dosing on Days 4 and 11.)
- Serum alkaline phosphatase(Assessments will be performed prior to dosing with telaglenastat on Days 2 and 9 and 24 hours after dosing on Days 4 and 11.)
- Serum Aspartate aminotransferase assessments(Assessments will be performed prior to dosing with telaglenastat on Days 2 and 9 and 24 hours after dosing on Days 4 and 11.)
- Serum aspartate aminotransferase(Assessments will be performed prior to dosing with telaglenastat on Days 2 and 9 and 24 hours after dosing on Days 4 and 11.)
- Serum albumin(Assessments will be performed prior to dosing with telaglenastat on Days 2 and 9 and 24 hours after dosing on Days 4 and 11.)
- Serum sodium(Assessments will be performed prior to dosing with telaglenastat on Days 2 and 9 and 24 hours after dosing on Days 4 and 11.)
- Incidence of changes in respiratory rate.(Respiratory rate will be assessed prior to dosing with telaglenastat on Days 2 and 9 and 24 hours after dosing on Days 4 and 11.)
- Incidence of changes in blood pressure(Blood pressure will be assessed prior to dosing with telaglenastat on Days 2 and 9 and 24 hours after dosing on Days 4 and 11.)
- Electrocardiograms (ECGs)(ECGs will be performed prior to and 4 hours after telaglenastat dosing on Days 3 and 10 and 24 hours after telaglenastat dosing on Days 4 and 11.)
- Hemoglobin assessments(Assessments will be performed prior to dosing with telaglenastat on Days 2 and 9 and 24 hours after dosing on Days 4 and 11.)
- Serum potassium(Assessments will be performed prior to dosing with telaglenastat on Days 2 and 9 and 24 hours after dosing on Days 4 and 11.)
- Serum chloride(Assessments will be performed prior to dosing with telaglenastat on Days 2 and 9 and 24 hours after dosing on Days 4 and 11.)
- Serum glucose(Assessments will be performed prior to dosing with telaglenastat on Days 2 and 9 and 24 hours after dosing on Days 4 and 11.)
- Serum creatinine(Assessments will be performed prior to dosing with telaglenastat on Days 2 and 9 and 24 hours after dosing on Days 4 and 11.)
- Urine pH(Assessments will be performed prior to dosing with telaglenastat on Days 2 and 9 and 24 hours after dosing on Days 4 and 11.)
- Urine Specific gravity(Assessments will be performed prior to dosing with telaglenastat on Days 2 and 9 and 24 hours after dosing on Days 4 and 11.)
- Urine Protein(Assessments will be performed prior to dosing with telaglenastat on Days 2 and 9 and 24 hours after dosing on Days 4 and 11.)
- Urine Glucose(Assessments will be performed prior to dosing with telaglenastat on Days 2 and 9 and 24 hours after dosing on Days 4 and 11.)
- Urine Ketones(Assessments will be performed prior to dosing with telaglenastat on Days 2 and 9 and 24 hours after dosing on Days 4 and 11.)
- Urine Bilirubin(Assessments will be performed prior to dosing with telaglenastat on Days 2 and 9 and 24 hours after dosing on Days 4 and 11.)
- Urine Blood(Assessments will be performed prior to dosing with telaglenastat on Days 2 and 9 and 24 hours after dosing on Days 4 and 11.)
- Urine Nitrite(Assessments will be performed prior to dosing with telaglenastat on Days 2 and 9 and 24 hours after dosing on Days 4 and 11.)
- Urine Urobilinogen(Assessments will be performed prior to dosing with telaglenastat on Days 2 and 9 and 24 hours after dosing on Days 4 and 11.)
- Urine Leukocyte esterase.(Assessments will be performed prior to dosing with telaglenastat on Days 2 and 9 and 24 hours after dosing on Days 4 and 11.)