Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12622000704796
Ethics application status
Approved
Date submitted
21/04/2022
Date registered
16/05/2022
Date last updated
20/03/2023
Date data sharing statement initially provided
16/05/2022
Date results information initially provided
20/03/2023
Type of registration
Prospectively registered

Titles & IDs
Public title
A Phase 1, Open-label, Multi-Period, Single Sequence Study to Evaluate the Relative Bioavailability, Performance, and Safety of Two Solid Oral Doses (Paltusotine Tablets) in Healthy Volunteers
Scientific title
A Phase 1, Open-label, Multi-Period, Single Sequence Study to Evaluate the Relative Bioavailability, Performance, and Safety of Two Solid Oral Doses (Paltusotine Tablets) in Healthy Volunteers
Secondary ID [1] 306596 0
CRN00808-20
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Acromegaly 325505 0
Condition category
Condition code
Metabolic and Endocrine 322880 322880 0 0
Other endocrine disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
The intervention for this study, paltusotine, is an orally bioavailable small molecule somatostatin receptor agonist that lowers growth hormone levels in acromegaly patients. Paltusotine will be supplied as 60 mg paltusotine tablets, test formulation, and 20 mg tablets, reference formulation.
The study will consist of 1 cohort in which participants will receive 1 dose of paltusotine (60 mg total), across 4 periods as follows:
Period 1: Participants to receive 1 dose of 3×20 mg tablet, reference formulation, after overnight fast with meal at 4 hours postdose.
Period 2: Participants to receive 1 dose of 1×60 mg tablet, test formulation, after overnight fast with meal at 4 hours postdose.
Period 3: Participants to receive 1 dose of 1×60 mg tablet, test formulation, after overnight fast with meal at 1 hour postdose.
Period 4: Participants to receive 1 dose of 1×60 mg tablet, test formulation, after overnight fast with meal at 4 hours postdose after pre-treatment with lansoprazole (orally disintegrating tablet, 15 mg twice daily) over 4 days. The final dose of lansoprazole will be taken at least 60 minutes prior to administration of the test formulation in Period 4.
A standard meal will be provided at least 4 hours after study drug administration for Periods 1, 2, and 4, and at least 1 hour after study drug administration for Period 3. The standard meal will provide a total of approximately 500 calories such that 36% of the calories (18 grams) are derived from fat, 14% from protein (16 grams) and 50% from carbohydrates (56 grams). An example test meal is 1 slice of toast (whole meal), 1 butter or margarine packet (as appropriate), 1 condiment packet (as appropriate), 1 cup of cereal/2 Weet-Bix with 250 mL milk, and 1 sugar sachet.
Participants will receive each dose with approximately 240 mL of water, after a 10 hour overnight fast. Participants will then fast for further 4 hours, or 1 hour for Period 3, after dosing. There will be 7 to 9 days between doses, except between Periods 3 and 4 there will be a 7-day washout. There will be up to 14 subjects enrolled in this study.
Dosing with Paltusotine for all periods will be administered by the study personnel at the research unit, and a mouth check will be conducted following dosing for each participant in all periods. Accountability records will be maintained by the study personnel to ensure compliance.
Randomization will not be applicable in this single sequence study. All participants will progress sequentially through Periods 1- 4 in the same order.
Intervention code [1] 323026 0
Treatment: Drugs
Comparator / control treatment
Active control for the study is the 20 mg Paltusotine reference tablet. Participants receive the active control in Period 1 of this 4-period study as 1 dose of of 3×20 mg tablet, reference formulation, after overnight fast with meal at 4 hours postdose.
Control group
Active

Outcomes
Primary outcome [1] 330664 0
Comparison of the pharmacokinetic profile of a 60 mg paltusotine single-tablet (test formulation) in Period 2, to 60 mg paltusotine as 3 x 20 mg tablets (reference formulation) in Period 1, as assessed by pharmacokinetic blood plasma concentration. Pharmacokinetic parameters include AUC, Cmax, Tmax, and t1/2.
Timepoint [1] 330664 0
Pharmacokinetic blood plasma sampling is to occur at the following timepoints:
Periods 1, 2, 3 and 4: within 30 min prior to paltusotine dosing, 15 min, 30 min, 45 min, 1 hr, 1.25 hrs, 1.5 hrs, 2.0 hrs, 3.0 hrs, 4.0 hrs, 6.0 hrs, 8.0 hrs, 10 hrs, 12 hrs, 24 hrs, 48 hrs, 96 hrs and 144 hrs post dose.
Primary outcome [2] 331299 0
Comparison of the pharmacokinetic profile of a 60 mg paltusotine single-tablet dose under different gastric conditions: 4 hour post-dose fasting in Period 2; 1-hour post dose fasting in Period 3; and reduced acidic levels after administration of Lansoprazole in Period 4, as assessed by pharmacokinetic blood plasma concentration. Pharmacokinetic parameters include AUC, Cmax, Tmax, and t1/2.
Timepoint [2] 331299 0
Pharmacokinetic blood plasma sampling is to occur at the following timepoints:
Periods 1, 2, 3 and 4: within 30 min prior to paltusotine dosing, 15 min, 30 min, 45 min, 1 hr, 1.25 hrs, 1.5 hrs, 2.0 hrs, 3.0 hrs, 4.0 hrs, 6.0 hrs, 8.0 hrs, 10 hrs, 12 hrs, 24 hrs, 48 hrs, 96 hrs and 144 hrs post dose.
Secondary outcome [1] 407111 0
Safety and tolerability of paltusotine tablets as assessed by Physical Examinations, 12 Lead ECG, Vital Sign measurements, Safety Laboratory tests, and adverse event assessments.
Timepoint [1] 407111 0
Physical Examinations will be performed at the following timepoints:
Screening, Period 1 Day -1, and Period 4 Day 7
12 Lead ECG will be performed in triplicate at the following timepoints:
Screening, Periods 1, 2, 3, and 4 Day -1, Day 1 pre-dose and 3 hrs post dose, Day 2 24 hrs post dose, and Day 7 (Period 4 only, final study visit).
Vital Signs, including Blood Pressure (via digital blood pressure monitor), Temperature (via digital tympanic thermometer) and, Heart Rate and Respiratory Rate (manual count), at the following timepoints: Screening, Periods 1, 2, 3, and 4 at Day -1, Day 1 pre-dose and 3 hrs post dose, Day 2 24 hrs post dose, and Day 7 (Period 4 only, final study visit).
Safety Laboratory tests, including Serum Chemistry, Haematology and urinalysis, will be performed at the following timepoints:
Screening, Periods 1, 2, 3 and 4 at Day -1, prior to breakfast on Day 2, and prior to breakfast on Day 7 (Period 4 only).
Adverse events will be recorded from the time that a subject signs consent until the final follow up visit. Site staff will question subjects on their health when conducting other assessments throughout the trial. Adverse events will be assessed by study investigators. Adverse events known to be associated with somatostatin receptor agonists include abdominal pain, diarrhea, and nausea.
Secondary outcome [2] 409472 0
Evaluation of the performance of the test formulation (60 mg tablet) in comparison with the exposure and profile of the current 20 mg tablet (reference formulation) to determine if the 60 mg tablet could be used to reduce patient pill burden. The performance is evaluated by pharmacokinetic exposures (e.g. Cmax and AUC) and pharmacokinetic profile (e.g. Tmax and T1/2).
Timepoint [2] 409472 0
Pharmacokinetic blood plasma sampling is to occur at the following timepoints:
Periods 1, 2, 3 and 4: within 30 min prior to paltusotine dosing, 15 min, 30 min, 45 min, 1 hr, 1.25 hrs, 1.5 hrs, 2.0 hrs, 3.0 hrs, 4.0 hrs, 6.0 hrs, 8.0 hrs, 10 hrs, 12 hrs, 24 hrs, 48 hrs, 96 hrs and 144 hrs post dose.

Eligibility
Key inclusion criteria
-Male and female subjects 18 to 65 years of age
-BMI 18 to 30 kg/m2
- Females must be non-pregnant and non-lactating, and either surgically sterile, post-menopausal, or must agree to use a highly effective or two clinically acceptable methods of contraception for the duration of the study and for 30 days after the last study visit.
- Male subjects must use a condom and his female partner of childbearing potential must use a highly effective or clinically acceptable form of contraception for the duration of the study and until at least 3 months after the last dose of study drug. Male subjects must also agree to not donate sperm for the duration of the study and until at least 3 months after the last dose of study drug.
-Willing to provide signed informed consent
Minimum age
18 Years
Maximum age
65 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
- Prior treatment with paltusotine.
- Any uncontrolled or active major systemic disease.
- History or presence of malignancy except adequately treated basal cell and squamous cell carcinomas of the skin within the past 5 years.
- Active acute or chronic infection.
- Had an unstable psychological disorder less than or equal to 1 year before screening based on the subject’s medical history.
- Had a medically significant illness within 30 days of admission.
- Use of any investigational drug within the past 60 days or 5 half-lives, whichever is longer prior to the first dosing of study drug.
- Use of any prior medication without approval of the Investigator within 14 days prior to admission.
- History of or current alcohol abuse.
- Heavy use of Tobacco and/or nicotine products.
- Taking moderate or strong CYP3A4 inhibitors or inducers.
- Poor CYP2C19 metabolizers, or ultrarapid metabolizers as determined from blood sample collected during Screening.
- Any condition that in the opinion of the investigator would jeopardize the subject's appropriate participation in the study.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised 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
Who is / are masked / blinded?



Intervention assignment
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
1/06/2022
Actual
1/06/2022
Date of last participant enrolment
Anticipated
15/06/2022
Actual
15/06/2022
Date of last data collection
Anticipated
14/07/2022
Actual
30/07/2022
Sample size
Target
14
Accrual to date
Final
18
Recruitment in Australia
Recruitment state(s)
SA

Funding & Sponsors
Funding source category [1] 310931 0
Commercial sector/Industry
Name [1] 310931 0
Crinetics Australia Pty Ltd
Country [1] 310931 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
Crinetics Australia Pty Ltd
Address
Crinetics Australia Pty Ltd 17 Praeger Street Chapel Hill, QLD 4069 Australia
Country
Australia
Secondary sponsor category [1] 312225 0
Commercial sector/Industry
Name [1] 312225 0
Avance Clinical Pty Ltd
Address [1] 312225 0
Avance Clinical Pty Ltd Level 1, 2 Ann Nelson Drive Thebarton, SA, 5043 Australia
Country [1] 312225 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 310487 0
Bellberry Limited, Committee G - EC00458
Ethics committee address [1] 310487 0
123 Glen Osmond Rd, Eastwood SA 5063
Ethics committee country [1] 310487 0
Australia
Date submitted for ethics approval [1] 310487 0
02/03/2022
Approval date [1] 310487 0
14/04/2022
Ethics approval number [1] 310487 0

Summary
Brief summary
Paltusotine is an oral somatostain receptor 2 (sst2) agonist being developed for the treatment of acromegaly. This single cohort, 4 period study will evaluate the relative bioavailability of 60 mg paltusotine tablet, test formulation, compared to 60 mg paltusotine tablet, reference formulation, in healthy volunteers.
The study will consist of 1 cohort in which participants will receive 1 dose of paltusotine (60 mg total), across 4 periods as follows:
Period 1: Participants to receive 1 dose of 3×20 mg tablet, reference formulation, after overnight fast with meal at 4 hours postdose.
Period 2: Participants to receive 1 dose of 1×60 mg tablet, test formulation, after overnight fast with meal at 4 hours postdose.
Period 3: Participants to receive 1 dose of 1×60 mg tablet, test formulation, after overnight fast with meal at 1 hour postdose.
Period 4: Participants to receive 1 dose of 1×60 mg tablet, test formulation, after overnight fast with meal at 4 hours postdose after pre-treatment with lansoprazole (orally disintegrating tablet, 15 mg twice daily) over 4 days.
Participants will receive each dose with approximately 240 mL of water, after a 10 hour overnight fast. Participants will then fast for further 4 hours, or 1 hour for Period 3, after dosing. There will be 7 to 9 days between doses, except between Periods 3 and 4 there will be a 7-day washout. There will be up to 14 subjects enrolled in this study.
Trial website
Trial related presentations / publications
Public notes
Positive COVID-19 rapid Antigen test is an exclusion criterion for this study.

Contacts
Principal investigator
Name 117842 0
Prof Sepehr Shakib
Address 117842 0
CMAX Clinical Research Pty Ltd Level 5, 21 North Terrace Adelaide, SA, 5000, Australia
Country 117842 0
Australia
Phone 117842 0
+61 441 100 278
Fax 117842 0
Email 117842 0
[email protected]
Contact person for public queries
Name 117843 0
Prof Sepehr Shakib
Address 117843 0
CMAX Clinical Research Pty Ltd Level 5, 21 North Terrace Adelaide, SA, 5000, Australia
Country 117843 0
Australia
Phone 117843 0
+61 441 100 278
Fax 117843 0
Email 117843 0
[email protected]
Contact person for scientific queries
Name 117844 0
Prof Sepehr Shakib
Address 117844 0
CMAX Clinical Research Pty Ltd Level 5, 21 North Terrace Adelaide, SA, 5000, Australia
Country 117844 0
Australia
Phone 117844 0
+61 441 100 278
Fax 117844 0
Email 117844 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.