Impact of a Histamine H2 Receptor Antagonist (H2RA) on the Pharmacokinetics (PK) of Telaglenastat in Healthy Subjects

NCT04540965 | Completed Phase 1 FDA Drug

• 1 other identifier: CX-839-015
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 1

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.

Conditions

Drug Interaction

Outcome Measures

Primary Outcomes (6)

• Peak Plasma Concentration (Cmax)

  To assess the effect of famotidine on the Cmax of telaglenastat in healthy adult subjects

  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

• Time to peak plasma concentration (Tmax)

  To assess the effect of famotidine on the Tmax of telaglenastat in healthy adult subjects

  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

• Area under the concentration-time curve from time = 0 to the last determination (AUClast)

  To assess the effect of famotidine on the time to maximum plasma concentration (Tmax) of telaglenastat in healthy adult subjects.

  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.

• Area under the concentration-time curve from time = 0 to infinity (AUC0-inf)

  To assess the effect of famotidine on the AUC0-inf of telaglenastat in healthy adult subjects

  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.

• Half-life

  To assess the effect of famotidine on the half-life of telaglenastat in healthy adult subjects

  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.

• Elimination rate

  To assess the effect of famotidine on the elimination rate of telaglenastat in healthy adult subjects

  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.

Secondary Outcomes (32)

• 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 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.

• 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.

Study Arms (2)

Telaglenastat and Famotidine

EXPERIMENTAL

Famotidine

Drug: Telaglenastat; Drug: Famotidine

Telaglenastat and Placebo for Famotidine

PLACEBO COMPARATOR

Placebo for famotidine

Drug: Telaglenastat; Drug: Placebo for famotidine

Interventions

Telaglenastat DRUG

Glutaminase inhibitor

Also known as: CB-839

Telaglenastat and Famotidine; Telaglenastat and Placebo for Famotidine

Famotidine DRUG

Histamine-H2 Receptor Antagonist

Also known as: Pepcid

Telaglenastat and Famotidine

Placebo for famotidine DRUG

Placebo for Histamine-H2 Receptor Antagonist

Telaglenastat and Placebo for Famotidine

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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 7.
• 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:
• must have undergone one of the following sterilization procedures at least 6 months prior to the first dose of any study drug:
• hysteroscopic sterilization;
• bilateral salpingectomy;
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• Women with a tubal ligation less than one year prior to study start must agree to use a barrier method of birth control 3. non-surgical transcervical sterilization (eg, Essure®); 4. hysterectomy; 5. bilateral oophorectomy OR

You may not qualify if:

• 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;
• seizures;
• 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;
• cardiovascular disease, cardiac arrhythmias, hypertension, cardiovascular thrombotic events, myocardial infarction, or stroke;
• ulcer disease or gastrointestinal bleeding;
• renal papillary necrosis and other renal injury;
• exfoliative dermatitis, Stevens-Johnson syndrome, and toxic epidermal necrolysis.

Sponsors & Collaborators

• Calithera Biosciences, Inc: lead
• Novotech (Australia) Pty Limited: collaborator

Study Sites (1)

Nucleus Network Brisbane Clinic (formerly Q-Pharm)

Brisbane, Queensland, Herston QLD 4006, Australia

Location

MeSH Terms

Interventions

CB-839; Famotidine

Intervention Hierarchy (Ancestors)

Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Paul Griffin, Dr.

  Nucleus Network

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Famotidine or Placebo for famotidine
• Purpose: OTHER
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 19, 2020
• First Posted: September 7, 2020
• Study Start: September 22, 2020
• Primary Completion: December 8, 2020
• Study Completion: December 8, 2020
• Last Updated: March 9, 2021

Record last verified: 2021-03

Locations

AU (1)