Cardiac SafetyPhase 1NCT04607512
Study to Evaluate the ECG Effects of Telaglenastat in Healthy Adult Subjects
A Phase 1 study testing telaglenastat and moxifloxicin in people with Cardiac Safety, run by Calithera Biosciences, Inc at 1 site in United Kingdom.
Trial summary
This study is designed to evaluate the effects of telaglenastat on cardiac repolarization (relative to placebo) in healthy adult subjects. Read more about this study
- Who is it for?
- Ages 18 to 45 yearsHealthy volunteers can take part
- Conditions the study is for
- Cardiac Safety
- What is being tested?
- telaglenastat and moxifloxicin
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 30 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 5 Oct 2020to 30 Dec 2020
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 45 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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;
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- 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.
Who cannot join
- 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.
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- 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.
- History or presence of:
- 1. Risk factors for Torsade de Pointes (eg, heart failure, cardiomyopathy, or family history of Long QT Syndrome or Brugada Syndrome) 2. Sick sinus syndrome, second or third degree atrioventricular block, myocardial infarction, pulmonary congestion, symptomatic or significant cardiac arrhythmia, prolonged QTcF, or clinically significant conduction abnormalities 3. History of angina, myocardial ischemia, arrythmia, heart failure or stroke 4. Clinically significant cardiac history or presence of ECG findings as judged by the PI or designee at screening or first check in, including the presence of abnormal sinus rhythm (HR < 50 or > 100 bpm; measurement may be repeated once at the discretion of the PI or designee) 17. Resting supine blood pressure is less than 90/50 mmHg or greater than 140/90 mmHg at the screening visit (may be repeated twice at the discretion of the PI or designee).
- 18. Unable to refrain from or anticipates the use of:
- Any drug, including prescription and non prescription medications (including gastric acid reducing [PPIs, histamine-2 receptor antagonists] or buffering agents [eg Tums]), herbal remedies, or vitamin supplements beginning 14 days prior to the first dosing and throughout the study. Medication listed as part of acceptable birth control methods will be allowed (refer to Section 11.1). After randomization/dosing, paracetamol (up to 2 g per 24 hours) may be administered at the discretion of the PI or designee.
- Any drugs known to be substrates of CYP2C9 (eg, warfarin) within 14 days prior to Day 1 and throughout the study. Appropriate sources (eg, Flockhart TableTM) will be consulted to confirm lack of PK/PD interaction with study drug.
- Food and beverages containing xanthines/caffeine (including energy drinks) for 24 hours prior to Day 1 of Period 1;
- Food and beverages containing alcohol for 48 hours prior to Day 1 of Period 1.
- Food and beverages containing grapefruit/Seville orange for 14 days prior to Day 1 of Period 1.
- 19. Has been on a diet incompatible with the on study diet, in the opinion of the PI or designee, within the 30 days prior to the first dosing and throughout the study.
- 20. Is lactose intolerant or has any significant food allergy, in the opinion of the PI or designee.
- 21. Donation of blood or plasma, or significant blood loss within 90 days prior to the first dosing.
- 22. Donation of bone marrow within the last 6 months prior to the first dosing. 23. Participation in another clinical study within 90 days prior to the first dosing. The 90 day window will be derived from the date of the last blood collection or dosing, whichever is later, in the previous study to Day 1 of Period 1 of the current study.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Three-Way Crossover Study to Evaluate the ECG Effects of Telaglenastat in Healthy Adult Subjects
This study is designed to evaluate the effects of telaglenastat on cardiac repolarization (relative to placebo) in healthy adult subjects.
Read the detailed description
This is a multiple-dose, randomized, double-blind (with respect to telaglenastat and placebo), placebo- and positive controlled, 3 way crossover thorough QT (TQT) study in healthy adult subjects.
On Day 1 of Period 1, subjects will be randomized to 1 of 6 treatment sequences.
In Treatments A and B, subjects will receive the assigned treatment on Day 1 through the morning of Day 4. In Treatment C, subjects will receive a single-dose administration of moxifloxacin in the morning of Day 4. Cardiodynamic readings will be collected for 24 hours on Days 1 and 4. Plasma PK samples will be collected prior to dosing (for Treatments A and B or Hour 0 for Treatment C) and up to 24 hours on Days 1 and 4 of all treatments.
- Conditions
- Cardiac Safety
- Being tested
- telaglenastat, telaglenastat placebo, moxifloxicin
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
telaglenastatDrug
glutaminase inhibitor
telaglenastat placeboOther
matching placebo for telaglenastat
moxifloxicinOther
positive control
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: 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 Receives: Other: telaglenastat placebo |
| Moxifloxacin | Active comparator | Single dose of 400 mg moxifloxacin (1 x 400 mg tablet) administered on the morning of Day 4 Receives: Other: moxifloxicin |
What is being measured
The primary outcome is the main question the study is designed to answer.
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)
Measured: 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.
Time-point change from baseline in QTc, placebo-adjusted and corrected for HR based on the Fridericia QT correction method (ΔΔQTcF)
Measured: 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.
Placebo-corrected ΔHR, ΔQTcF, ΔPR, and ΔQRS (ΔΔHR, ∆∆QTcF, ΔΔPR, and ΔΔQRS) evaluated at each post baseline time point ('by time point' analysis)
Measured: 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.
Frequency of treatment emergent changes of T-wave morphology and U wave presence
Measured: 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.
- Evaluation of the relationship between the plasma concentration of moxifloxacin and ΔΔQTc in order to demonstrate assay sensitivity.
Measured: 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
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Oct 2020
- Study start5 Oct 2020
- Primary completion30 Dec 2020
- Study completion30 Dec 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Cardiac SafetyStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Crossover
- Model description
- double-blind (with respect to telaglenastat and placebo), placebo- and positive controlled, 3 way crossover
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 30 participants (actual)
Sponsor and investigators
- Lead sponsor
- Calithera Biosciences, Inc
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Sunu Valasseri, MD, Principal investigator, Celerion
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04607512
- Sponsor's protocol ID
- CX-839-013
- Status last verified
- Mar 2021
- First submitted
- 20 Oct 2020
- Last updated
- 9 Mar 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 9 Mar 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Three-Way Crossover Study to Evaluate the ECG Effects of Telaglenastat in Healthy Adult Subjects
- ClinicalTrials.gov ID
- NCT04607512
- Acronym / sponsor ID
- CX-839-013
- Conditions
- Cardiac Safety
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 30 participants (actual)
- Lead sponsor
- Calithera Biosciences, IncIndustry (pharma, biotech, devices)
- Study start
- 5 Oct 2020 (actual)
- Primary completion
- 30 Dec 2020 (actual)
- Study completion
- 30 Dec 2020 (actual)
- First posted
- 29 Oct 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study is designed to evaluate the effects of telaglenastat on cardiac repolarization (relative to placebo) in healthy adult subjects.
Detailed description
This is a multiple-dose, randomized, double-blind (with respect to telaglenastat and placebo), placebo- and positive controlled, 3 way crossover thorough QT (TQT) study in healthy adult subjects.
On Day 1 of Period 1, subjects will be randomized to 1 of 6 treatment sequences.
In Treatments A and B, subjects will receive the assigned treatment on Day 1 through the morning of Day 4. In Treatment C, subjects will receive a single-dose administration of moxifloxacin in the morning of Day 4. Cardiodynamic readings will be collected for 24 hours on Days 1 and 4. Plasma PK samples will be collected prior to dosing (for Treatments A and B or Hour 0 for Treatment C) and up to 24 hours on Days 1 and 4 of all treatments.
Study design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
- Model description
- double-blind (with respect to telaglenastat and placebo), placebo- and positive controlled, 3 way crossover
| Arm | Type | Receives |
|---|---|---|
| Telaglenastat | Experimental | Drug: telaglenastat800 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 |
| Telaglenastat Placebo | Placebo comparator | Other: telaglenastat placebo800 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 |
| Moxifloxacin | Active comparator | Other: moxifloxicinSingle dose of 400 mg moxifloxacin (1 x 400 mg tablet) administered on the morning of Day 4 |
Who may qualify
- Ages
- 18 to 45 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (13 listed)
- 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:
Key exclusion criteria (27 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| telaglenastatglutaminase inhibitor | Drug | Telaglenastat |
| telaglenastat placebomatching placebo for telaglenastat | Other | Telaglenastat Placebo |
| moxifloxicinpositive control | Other | Moxifloxacin |
Primary outcome
To assess the effects of telaglenastat on cardiac repolarization (relative to placebo) using the therapeutic dose and schedule in healthy adult subjects
Time frame: 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
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)
4 secondary outcomes
To assess the effects of telaglenastat on heart rate (relative to placebo) using the therapeutic dose and schedule in healthy adult subjects.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Mar 2021.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Sunu Valasseri, MD principal investigator
Celerion
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing telaglenastat and moxifloxicin in people with Cardiac Safety, run by Calithera Biosciences, Inc at 1 site in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 13 inclusion and 27 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 9 Mar 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
To assess the effects of telaglenastat on cardiac repolarization (relative to placebo) using the therapeutic dose and schedule in healthy adult subjects (time frame: 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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Mar 2021; AzTrials last refreshed its copy on 8 Nov 2026.