Study to Evaluate the ECG Effects of Telaglenastat in Healthy Adult Subjects

NCT04607512 | Completed Phase 1 FDA Drug

• 1 other identifier: CX-839-013
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

This study is designed to evaluate the effects of telaglenastat on cardiac repolarization (relative to placebo) in healthy adult subjects.

Conditions

Cardiac Safety

Outcome Measures

Primary Outcomes (1)

• To assess the effects of telaglenastat on cardiac repolarization (relative to placebo) using the therapeutic dose and schedule in healthy adult subjects

  Evaluation of the relationship between the plasma concentrations of telaglenastat and its metabolite 110826 with the ΔQTc, placebo-adjusted and corrected for HR based on the Fridericia QT correction method (ΔΔQTcF)

  Plasma samples and triplicate ECGs taken on Days 1 and 4 of each period at baseline, 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 16 and 24 hours post administration

Secondary Outcomes (4)

• To assess the effects of telaglenastat on heart rate (relative to placebo) using the therapeutic dose and schedule in healthy adult subjects.

  Triplicate ECGs taken on Days 1 and 4 of each period at baseline, 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 16 and 24 hours post administration

• To assess the effects of telaglenastat on other ECG parameters (relative to placebo) using the therapeutic dose and schedule in healthy adult subjects.

  Triplicate ECGs taken on Days 1 and 4 of each period at baseline, 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 16 and 24 hours post administration

• To assess the effects of telaglenastat on changes of T-wave morphology and U wave presence (relative to placebo) using the therapeutic dose and schedule in healthy adult subjects.

  Triplicate ECGs taken on Days 1 and 4 of each period at baseline, 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 16 and 24 hours post administration

• To demonstrate sensitivity of this QTc assay using moxifloxacin as a positive control.

  Triplicate ECGs taken on Days 1 and 4 of each period at baseline, 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 16 and 24 hours post administration

Study Arms (3)

Telaglenastat

EXPERIMENTAL

800 mg telaglenastat (4 x 200 mg tablets) administered twice daily (BID) on Days 1 3, with a single dose administered on the morning of Day 4

Drug: telaglenastat

Telaglenastat Placebo

PLACEBO COMPARATOR

800 mg placebo (4 x 200 mg tablets) administered twice daily (BID) on Days 1 3, with a single dose administered on the morning of Day 4

Other: telaglenastat placebo

Moxifloxacin

ACTIVE COMPARATOR

Single dose of 400 mg moxifloxacin (1 x 400 mg tablet) administered on the morning of Day 4

Other: moxifloxicin

Interventions

telaglenastat DRUG

glutaminase inhibitor

Telaglenastat

telaglenastat placebo OTHER

matching placebo for telaglenastat

Telaglenastat Placebo

moxifloxicin OTHER

positive control

Moxifloxacin

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy, adult, male or female (of non childbearing potential only), 18-45 years of age, inclusive, at the screening visit.
• Continuous non smoker who has not used nicotine containing products (chewed or smoked) or replacement products, including electronic cigarettes, for at least 3 months prior to the first dosing and throughout the study, and have a negative cotinine test result at the screening and check-in visits.
• Body mass index (BMI) ≥ 18 and ≤ 28.0 kg/m2 at the screening visit.
• Medically healthy with no clinically significant medical history, physical examination, laboratory profiles, vital signs or ECGs, as deemed by the PI or designee.
• A female of non childbearing potential has undergone one of the following sterilization procedures at least 6 months prior to the first dosing:
• hysteroscopic sterilization;
• bilateral salpingectomy;
• hysterectomy;
• bilateral oophorectomy. or be postmenopausal with amenorrhea for at least 1 year prior to the first dosing and follicle stimulating hormone (FSH) serum levels consistent with postmenopausal status.
• A non vasectomized, male subject must agree to use a condom with spermicide or abstain from sexual intercourse during the study until 90 days after the last dosing. (No restrictions are required for a vasectomized male provided his vasectomy has been performed 4 months or more prior to the first dosing. A male who has been vasectomized less than 4 months prior to study first dosing must follow the same restrictions as a non vasectomized male).
• If male, must agree not to donate sperm from the first dosing until 90 days after the last dosing.
• Able and willing to swallow whole tablets without breaking, cutting or chewing.
• Understands the study procedures in the informed consent form (ICF) and is willing and able to comply with the protocol.

You may not qualify if:

• History or presence of diseases which, as judged by the investigator, may affect the outcome of this study, including but not limited to significant cardiovascular, pulmonary, hepatic, renal, hematological, gastrointestinal, endocrine, immunologic, dermatologic, or neurologic disease.
• History or presence of clinically significant medical or psychiatric condition or disease in the opinion of the PI or designee.
• History of hospitalization for a major illness or procedure in the last 3 months. Subjects with preplanned and elective surgery or a procedure that requires inpatient hospitalization throughout the duration of the study are excluded from the study.
• History of any illness that, in the opinion of the PI or designee, might confound the results of the study or pose an additional risk to the subject by their participation in the study.
• Any condition that may interfere with the absorption, metabolism, or elimination of telaglenastat.
• Clinically significant laboratory values that would place the subject at undue risk in the opinion of the PI or designee, including but not limited to serum alanine aminotransferase (ALT) or serum aspartate aminotransferase (AST) \> 1.2 × upper limit of normal at the screening visit.
• History or presence of alcohol or drug abuse within the past 2 years prior to the first dosing.
• History or presence of hypersensitivity or idiosyncratic reaction to the study drug(s) or related compounds.
• History of tendon disease/disorder related to quinolone treatment.
• Female subjects with a positive pregnancy test at the screening visit or first check in or who are lactating.
• Positive urine drug or alcohol results at the screening visit or first check in.
• Regular use of alcohol within 6 months prior to the screening visit (more than 21 units of alcohol per week for men, or 14 units of alcohol per week for women \[1 Unit = 150 mL of wine, 360 mL of beer, or 45 mL of 40% alcohol\]).
• Use of recreational drugs (such as marijuana) within three months prior to the screening visit or illicit drugs (such as cocaine or methamphetamine) within one year prior to the screening visit.
• Positive results at the screening visit for human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg), or hepatitis C virus (HCV).
• Family history of QTc prolongation or of unexplainable sudden death at \< 50 years of age.

Sponsors & Collaborators

• Calithera Biosciences, Inc: lead

Study Sites (1)

Celerion

Belfast, Ireland, BT9 6AD, United Kingdom

Location

Study Officials

• Sunu Valasseri, MD

  Celerion

  PRINCIPAL INVESTIGATOR

Study Design

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

Model Details: double-blind (with respect to telaglenastat and placebo), placebo- and positive controlled, 3 way crossover

Study Record Dates

• First Submitted: October 20, 2020
• First Posted: October 29, 2020
• Study Start: October 5, 2020
• Primary Completion: December 30, 2020
• Study Completion: December 30, 2020
• Last Updated: March 9, 2021

Record last verified: 2021-03

Locations

GB (1)