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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT04540965




Registration number
NCT04540965
Ethics application status
Date submitted
19/08/2020
Date registered
7/09/2020
Date last updated
9/03/2021

Titles & IDs
Public title
Impact of a Histamine H2 Receptor Antagonist (H2RA) on the Pharmacokinetics (PK) of Telaglenastat in Healthy Subjects
Scientific title
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
Secondary ID [1] 0 0
CX-839-015
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Drug Interaction 0 0
Condition category
Condition code

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Telaglenastat
Treatment: Drugs - Famotidine
Treatment: Drugs - Placebo for famotidine

Experimental: Telaglenastat and Famotidine - Famotidine

Placebo Comparator: Telaglenastat and Placebo for Famotidine - Placebo for famotidine


Treatment: Drugs: Telaglenastat
Glutaminase inhibitor

Treatment: Drugs: Famotidine
Histamine-H2 Receptor Antagonist

Treatment: Drugs: Placebo for famotidine
Placebo for Histamine-H2 Receptor Antagonist

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Peak Plasma Concentration (Cmax) - To assess the effect of famotidine on the Cmax of telaglenastat in healthy adult subjects
Timepoint [1] 0 0
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
Primary outcome [2] 0 0
Time to peak plasma concentration (Tmax) - To assess the effect of famotidine on the Tmax of telaglenastat in healthy adult subjects
Timepoint [2] 0 0
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
Primary outcome [3] 0 0
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.
Timepoint [3] 0 0
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.
Primary outcome [4] 0 0
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
Timepoint [4] 0 0
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.
Primary outcome [5] 0 0
Half-life - To assess the effect of famotidine on the half-life of telaglenastat in healthy adult subjects
Timepoint [5] 0 0
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.
Primary outcome [6] 0 0
Elimination rate - To assess the effect of famotidine on the elimination rate of telaglenastat in healthy adult subjects
Timepoint [6] 0 0
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 outcome [1] 0 0
Incidence of Treatment-Emergent Adverse Events - Assessed by physician reports of any unfavorable and unintended sign, symptom, or disease (new or exacerbated) that is temporally associated with the use of the investigational products.
Timepoint [1] 0 0
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.
Secondary outcome [2] 0 0
Incidence of changes in body temperature - Body temperature is measured in degrees Celsius.
Timepoint [2] 0 0
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.
Secondary outcome [3] 0 0
Incidence of changes in respiratory rate. - Respiratory rate is measured in breaths per minute.
Timepoint [3] 0 0
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.
Secondary outcome [4] 0 0
Incidence of changes in blood pressure - Blood pressure is measured in mmHg.
Timepoint [4] 0 0
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.
Secondary outcome [5] 0 0
Incidence of changes in heart rate. - Heart rate is measured in beats per minute.
Timepoint [5] 0 0
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.
Secondary outcome [6] 0 0
Electrocardiograms (ECGs) - Triplicate 12-lead ECGs including P Wave, QRS Complex, and QTcF determination
Timepoint [6] 0 0
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.
Secondary outcome [7] 0 0
Hemoglobin assessments - Hemoglobin will be measured in g/dL
Timepoint [7] 0 0
Assessments will be performed prior to dosing with telaglenastat on Days 2 and 9 and 24 hours after dosing on Days 4 and 11.
Secondary outcome [8] 0 0
Hematocrit assessments - Hematocrit will be measured in %
Timepoint [8] 0 0
Assessments will be performed prior to dosing with telaglenastat on Days 2 and 9 and 24 hours after dosing on Days 4 and 11.
Secondary outcome [9] 0 0
Leukocyte count assessments - Leukocyte count will be measured in 1000 cells/microliter
Timepoint [9] 0 0
Assessments will be performed prior to dosing with telaglenastat on Days 2 and 9 and 24 hours after dosing on Days 4 and 11.
Secondary outcome [10] 0 0
Red blood cell count assessments - Red blood cell count will be measured in 1,000,000 cells/microliter
Timepoint [10] 0 0
Assessments will be performed prior to dosing with telaglenastat on Days 2 and 9 and 24 hours after dosing on Days 4 and 11.
Secondary outcome [11] 0 0
Platelet count assessments - Platelet count.will be measured in 1000 cells/microliter
Timepoint [11] 0 0
Assessments will be performed prior to dosing with telaglenastat on Days 2 and 9 and 24 hours after dosing on Days 4 and 11.
Secondary outcome [12] 0 0
Serum urea - Serum Urea will be measured in mg/dL
Timepoint [12] 0 0
Assessments will be performed prior to dosing with telaglenastat on Days 2 and 9 and 24 hours after dosing on Days 4 and 11.
Secondary outcome [13] 0 0
Serum bilirubin - Serum Bilirubin will be measured in micromoles/L
Timepoint [13] 0 0
Assessments will be performed prior to dosing with telaglenastat on Days 2 and 9 and 24 hours after dosing on Days 4 and 11.
Secondary outcome [14] 0 0
Serum alkaline phosphatase - Serum alkaline phosphatase will be measured in units/L
Timepoint [14] 0 0
Assessments will be performed prior to dosing with telaglenastat on Days 2 and 9 and 24 hours after dosing on Days 4 and 11.
Secondary outcome [15] 0 0
Serum Aspartate aminotransferase assessments - Serum Aspartate aminotransferase will be measured in units/L
Timepoint [15] 0 0
Assessments will be performed prior to dosing with telaglenastat on Days 2 and 9 and 24 hours after dosing on Days 4 and 11.
Secondary outcome [16] 0 0
Serum aspartate aminotransferase - Serum Alanine aminotransferase will be measured in units/L
Timepoint [16] 0 0
Assessments will be performed prior to dosing with telaglenastat on Days 2 and 9 and 24 hours after dosing on Days 4 and 11.
Secondary outcome [17] 0 0
Serum albumin - Serum Albumin will be measured in g/dL
Timepoint [17] 0 0
Assessments will be performed prior to dosing with telaglenastat on Days 2 and 9 and 24 hours after dosing on Days 4 and 11.
Secondary outcome [18] 0 0
Serum sodium - Serum Sodium will be measured in meq/L
Timepoint [18] 0 0
Assessments will be performed prior to dosing with telaglenastat on Days 2 and 9 and 24 hours after dosing on Days 4 and 11.
Secondary outcome [19] 0 0
Serum potassium - Serum Potassium will be measured in meq/L
Timepoint [19] 0 0
Assessments will be performed prior to dosing with telaglenastat on Days 2 and 9 and 24 hours after dosing on Days 4 and 11.
Secondary outcome [20] 0 0
Serum chloride - Serum Chloride will be measured in meq/L
Timepoint [20] 0 0
Assessments will be performed prior to dosing with telaglenastat on Days 2 and 9 and 24 hours after dosing on Days 4 and 11.
Secondary outcome [21] 0 0
Serum glucose - Serum Glucose will be measured in mg/dL
Timepoint [21] 0 0
Assessments will be performed prior to dosing with telaglenastat on Days 2 and 9 and 24 hours after dosing on Days 4 and 11.
Secondary outcome [22] 0 0
Serum creatinine - Serum Creatinine will be measured in mg/dL
Timepoint [22] 0 0
Assessments will be performed prior to dosing with telaglenastat on Days 2 and 9 and 24 hours after dosing on Days 4 and 11.
Secondary outcome [23] 0 0
Urine pH - Urine pH will be measured in units
Timepoint [23] 0 0
Assessments will be performed prior to dosing with telaglenastat on Days 2 and 9 and 24 hours after dosing on Days 4 and 11.
Secondary outcome [24] 0 0
Urine Specific gravity - Urine Specific gravity will be measured in g/mL
Timepoint [24] 0 0
Assessments will be performed prior to dosing with telaglenastat on Days 2 and 9 and 24 hours after dosing on Days 4 and 11.
Secondary outcome [25] 0 0
Urine Protein - Urine Protein will be measured in mg/24 hr
Timepoint [25] 0 0
Assessments will be performed prior to dosing with telaglenastat on Days 2 and 9 and 24 hours after dosing on Days 4 and 11.
Secondary outcome [26] 0 0
Urine Glucose - Urine Glucose will be measured in mg/dL
Timepoint [26] 0 0
Assessments will be performed prior to dosing with telaglenastat on Days 2 and 9 and 24 hours after dosing on Days 4 and 11.
Secondary outcome [27] 0 0
Urine Ketones - Urine Ketones will be measured in mg/dL
Timepoint [27] 0 0
Assessments will be performed prior to dosing with telaglenastat on Days 2 and 9 and 24 hours after dosing on Days 4 and 11.
Secondary outcome [28] 0 0
Urine Bilirubin - Urine Bilirubin will be measured in mg/dL
Timepoint [28] 0 0
Assessments will be performed prior to dosing with telaglenastat on Days 2 and 9 and 24 hours after dosing on Days 4 and 11.
Secondary outcome [29] 0 0
Urine Blood - Urine Blood will be measured in RBC/high powered field
Timepoint [29] 0 0
Assessments will be performed prior to dosing with telaglenastat on Days 2 and 9 and 24 hours after dosing on Days 4 and 11.
Secondary outcome [30] 0 0
Urine Nitrite - Urine Nitrite will be measured by dipstick
Timepoint [30] 0 0
Assessments will be performed prior to dosing with telaglenastat on Days 2 and 9 and 24 hours after dosing on Days 4 and 11.
Secondary outcome [31] 0 0
Urine Urobilinogen - Urine Urobilinogen will be measured in Ehrlich units
Timepoint [31] 0 0
Assessments will be performed prior to dosing with telaglenastat on Days 2 and 9 and 24 hours after dosing on Days 4 and 11.
Secondary outcome [32] 0 0
Urine Leukocyte esterase. - Urine Leukocyte esterase will be measured in units
Timepoint [32] 0 0
Assessments will be performed prior to dosing with telaglenastat on Days 2 and 9 and 24 hours after dosing on Days 4 and 11.

Eligibility
Key inclusion criteria
1. Healthy adult male or female, 18-55 years of age, inclusive, at screening.

2. 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.

3. Body mass index (BMI) between 18.0 and 32.0 kg/m2, inclusively, at screening.

4. Medically healthy with no clinically significant medical history, physical
examination, laboratory profiles, vital signs, or ECGs, as deemed by the Principal
Investigator (PI).

5. 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:

1. 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.

2. 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.

6. 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.

7. Females of non-childbearing potential as defined below do not require contraception.

Females of non-childbearing potential:

1. must have undergone one of the following sterilization procedures at least 6
months prior to the first dose of any study drug:

1. hysteroscopic sterilization;

2. bilateral salpingectomy;

1. 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

2. be postmenopausal with amenorrhea for at least 1 year prior to the first
telaglenastat dose with follicle-stimulating hormone (FSH) serum levels > 30
IU/mL.

8. A non-vasectomized male subject must agree to use a physical barrier (eg, condom or
diaphragm) or abstain from sexual intercourse with female partners during the study
until the last dose of any study drug. (No restrictions are required for a
vasectomized male provided his vasectomy has been performed 4 months or more prior to
study start. A male who has been vasectomized less than 4 months prior to study start
must follow the same restrictions as a non-vasectomized male).

a) Female participants with a vasectomized male partner, or male participants with a
female partner of non-childbearing potential do not require contraception.

9. If male, must agree not to donate sperm from dosing until the last dose of any study
drug.

10. Alanine and aspartate aminotransferase and bilirubin levels = the upper limit of
normal or deemed not clinically significant by the Investigator.

11. Understands the study procedures in the informed consent form (ICF) and be willing and
able to comply with the protocol.
Minimum age
18 Years
Maximum age
55 Years
Gender
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
1. 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.

2. History or presence of clinically significant medical or psychiatric condition or
disease in the opinion of the PI.

3. 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.

4. History or presence of alcoholism or drug abuse within the past 2 years prior to
screening.

5. History or presence of hypersensitivity or idiosyncratic reaction to the study drugs
or inactive ingredient(s).

6. History or presence of:

1. liver disease, pancreatic insufficiency or intestinal malabsorption;

2. neuropathy or muscle disorders;

3. seizures;

4. asthma; childhood asthma that has resolved and has not required medical treatment
for at least 5 years prior to study start is permitted;

5. fluid retention;

6. cardiovascular disease, cardiac arrhythmias, hypertension, cardiovascular
thrombotic events, myocardial infarction, or stroke;

7. ulcer disease or gastrointestinal bleeding;

8. renal papillary necrosis and other renal injury;

9. exfoliative dermatitis, Stevens-Johnson syndrome, and toxic epidermal necrolysis.

7. Female subjects who are pregnant or lactating.

8. Positive urine drug or alcohol results at screening or check-in.

9. Positive urine cotinine at screening or check-in.

10. Positive results at screening for HIV types 1 and 2, HBsAg, or hepatitus C virus.

11. Seated blood pressure (taken after 5 minutes in a sitting position) is less than 90/40
mmHg or greater than 140/90 mmHg at screening and not as part of ECG.

12. Seated heart rate (taken after 5 minutes in a sitting position) is lower than 40 bpm
or higher than 100 bpm at screening and not as part of ECG.

13. QTcF interval is > 460 msec (males) or > 480 msec (females) or deemed clinically
abnormal by the PI at screening.

14. Estimated creatinine clearance < 90 mL/min calculated by the method of Cockcroft and
Gault at screening.

15. Unable to refrain from or anticipates the use of:

1. Proton pump inhibitors (PPIs), histamine H2 receptor antagonists (H2RAs),
buffering agents (eg, Tums) or any other medication that may have an effect on
gastric acid secretion beginning 14 days prior to the first dose of any study
drug and throughout the study.

2. Any non-prescription medications, herbal remedies, or vitamin supplements
beginning 14 days prior to the first dose of any study drug and throughout the
study.

3. Any prescription medications (including hormone replacement therapy and lithium)
beginning 14 days prior to the first dose of any study drug and throughout the
study.

16. Donation of blood or significant blood loss within 56 days prior to the first dose of
any study drug.

17. Plasma donation within 14 days prior to the first dose of any study drug.

18. Presence of any medical history or condition that may limit gastric drug absorption
(eg, prior gastric surgery, gastric banding, Whipple procedure)

19. Participation in another clinical trial within 28 days prior to the first dose of any
study drug. The 28-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.

Study design
Purpose of the study
Other
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Crossover
Other design features
Phase
Phase 1
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
QLD
Recruitment hospital [1] 0 0
Nucleus Network Brisbane Clinic (formerly Q-Pharm) - Brisbane
Recruitment postcode(s) [1] 0 0
Herston QLD 4006 - Brisbane

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Calithera Biosciences, Inc
Address
Country
Other collaborator category [1] 0 0
Commercial sector/Industry
Name [1] 0 0
Novotech (Australia) Pty Limited
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/show/NCT04540965
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Paul Griffin, Dr.
Address 0 0
Nucleus Network
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
Other publications