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Trial registered on ANZCTR


Registration number
ACTRN12618001646235
Ethics application status
Approved
Date submitted
28/09/2018
Date registered
4/10/2018
Date last updated
25/02/2019
Date data sharing statement initially provided
25/02/2019
Date results information initially provided
25/02/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
An open label, single cohort, randomized, 4-period crossover Phase 1 study to determine the effect of meal timing relative to CRN00808 administration on the safety and pharmacokinetics of CRN00808 in healthy volunteers
Scientific title
An open label, single cohort, randomized, 4-period crossover Phase 1 study to determine the effect of meal timing relative to CRN00808 administration on the safety and pharmacokinetics of CRN00808 in healthy volunteers
Secondary ID [1] 295693 0
Protocol Number: CRN00808-04
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Acromegaly 309068 0
Condition category
Condition code
Metabolic and Endocrine 307953 307953 0 0
Other endocrine disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
The intervention for this study, CRN00808, is an orally bioavailable small molecule somatostatin receptor agonist that lowers hormone levels in acromegaly patients. CRN00808 will be administered as a 2 x 10mg capsules for a total dose of 20mg in all four periods.
This study consists of 4 administration conditions:
Condition A: Subjects will remain fasting for 4 hours after drug administration.
Condition B: Subjects will remain fasting for 2 hours after drug administration.
Condition C: Subjects will remain fasting for 1 hour after drug administration.
Condition D: Subjects will receive a standard dinner then fast for 2 hours prior to drug administration. After dosing, the subject will fast overnight.
Subjects will be directly observed by study personnel to ensure that the fasting requirements are adhered to. The Condition D standard dinner will be nutritionally identical for all subjects, however the meal may differ to accommodate subjects with dietary requirements, such as; vegetarian, vegan and gluten free.
There will be up to 12 subjects enrolled in this study. All subjects will be administered study drug under each of the four conditions. There will be 8 days between treatment administration for each condition.
Subjects will undergo Condition A, B and C in a randomised order. Condition D will be completed by all subjects after completion of Condition A, B and C.
Intervention code [1] 302012 0
Treatment: Drugs
Comparator / control treatment
This is a four-period crossover study in which all participants receive the same condition in the fourth period
Control group
Active

Outcomes
Primary outcome [1] 306930 0
Pharmacokinetics parameters (AUC, Cmax, Tmax, Tlag and T1/2) following single doses of CRN00808 in male and female subjects derived from plasma concentrations of CRN00808.
Timepoint [1] 306930 0
PK Plasma sampling, collected at the following timepoints;
15 mins pre-dose, 15 mins, 30 mins, 45 mins, 1 hr, 1.25 hr, 1.5 hr, 2.0 hr, 3.0 hr, 4.0 hr, 6.0 hr, 8.0 hr, 10 hr, 12 hr, 18 hr, 24 hr, 72 hr, 120 hr post dosing in each period. A final sample will also be collected on Day 33.
Secondary outcome [1] 350147 0
Safety and tolerability of single doses of CRN00808 in male and female subjects based on clinical laboratory tests, triplicate ECGs, vital signs, physical exams and adverse events.
Timepoint [1] 350147 0
Clinical laboratory tests including chemistry, haematology and urinalysis at the following time points;
Screening, Check in, Day 2 post dose and Day 6 post dose for each period. Clinical laboratory tests will also be performed at Day 33.
triplicate ECGs at the following timepoints;
Screening, check in, pre-dose, 3.0 hrs, and 24 hrs post dose for each period, Triplicate ECGs will also be performed on Day 33.
Vital signs at the following timepoints;
Screening, check in, predose, 1.5 hrs, 3.0 hrs, 6.0 hrs and 24 hrs post-dose for each period. Vital signs will also be performed on Day 33.
Physical exams at the following timepoints;
Screening, check in for every period and on Day 33.
Adverse events will be recorded from the time that a subject signs consent until the final follow up visit on day 33. 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.

Eligibility
Key inclusion criteria
- Male and female subjects 18 to 70 years of age
- BMI 18 to 30 kg/m2
- Females must be non-pregnant and non-lactating, and either surgically sterile, post-
menopausal, or using effective method(s) of birth control
- Willing to provide signed informed consent
Minimum age
18 Years
Maximum age
70 Years
Gender
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
- Prior treatment with CRN00808
- Any uncontrolled or active major systemic disease which makes study participation
unsafe or could interfere with evaluation of the endpoints of the study.
- History or presence of malignancy except adequately treated basal cell and squamous
cell carcinomas of the skin within the past 5 years.
- Use of any investigational drug within the past 60 days
- Have a medically significant abnormality observed during screening or the admission physical examination or in any other baseline measurements
- Use of any prior medication without approval of the investigator within 14 days prior to admission
- Tested positive at screening for HIV, hepatitis B surface antigen (HBsAg) or hepatitis C antibody (HCV-Ab) or has a history of a positive result
- History of alcohol or substance abuse in the past 12 months
- Any condition that in the opinion of the investigator would jeopardize the subject's appropriate participation in this Phase 1 study

Study design
Purpose of the study
Treatment
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
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Crossover
Other design features
This is a four-period crossover study in which all participants receive the same condition in the fourth period
Phase
Phase 1
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Completed
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)
VIC
Recruitment hospital [1] 11635 0
Nucleus Network - Melbourne
Recruitment postcode(s) [1] 23681 0
3004 - Melbourne

Funding & Sponsors
Funding source category [1] 300276 0
Commercial sector/Industry
Name [1] 300276 0
Crinetics Australia Pty Ltd
Address [1] 300276 0
Crinetics Australia Pty Ltd
17 Praeger Street
Chapel Hill, QLD 4069
Australia
Country [1] 300276 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] 299706 0
Commercial sector/Industry
Name [1] 299706 0
CPR Pharma Services Pty. Ltd.
Address [1] 299706 0
CPR Pharma Services Pty. Ltd.
28 Dalgleish Street
Thebarton, SA 5031
Australia
Country [1] 299706 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 301090 0
Bellberry Human Research Ethics Committee B (EC00419)
Ethics committee address [1] 301090 0
129 Glen Osmond Road
Eastwood SA 5063
Ethics committee country [1] 301090 0
Australia
Date submitted for ethics approval [1] 301090 0
13/08/2018
Approval date [1] 301090 0
07/09/2018
Ethics approval number [1] 301090 0
2018-08-639

Summary
Brief summary
CRN00808 is being developed for the treatment of acromegaly. This four-way crossover single dose study will compare the pharmacokinetic and safety profiles of CRN00808 over four periods under the following dosing conditions;
Condition A: Subjects will remain fasting for 4 hours after drug administration.
Condition B: Subjects will remain fasting for 2 hours after drug administration.
Condition C: Subjects will remain fasting for 1 hour after drug administration.
Condition D: Subjects will receive a standard dinner then fast for 2 hours prior to drug administration. After dosing, the subject will fast overnight.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 85850 0
Dr Jason Lickliter
Address 85850 0
Nucleus Network
Burnet Tower, AMREP Precinct
89 Commercial Road
Melbourne, VIC 3004
Australia
Country 85850 0
Australia
Phone 85850 0
+61 407 527 307
Fax 85850 0
Email 85850 0
j.lickliter@nucleusnetwork.com.au
Contact person for public queries
Name 85851 0
Dr Jason Lickliter
Address 85851 0
Nucleus Network
Burnet Tower, AMREP Precinct
89 Commercial Road
Melbourne, VIC 3004
Australia
Country 85851 0
Australia
Phone 85851 0
+61 407 527 307
Fax 85851 0
Email 85851 0
j.lickliter@nucleusnetwork.com.au
Contact person for scientific queries
Name 85852 0
Dr Jason Lickliter
Address 85852 0
Nucleus Network
Burnet Tower, AMREP Precinct
89 Commercial Road
Melbourne, VIC 3004
Australia
Country 85852 0
Australia
Phone 85852 0
+61 407 527 307
Fax 85852 0
Email 85852 0
j.lickliter@nucleusnetwork.com.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
No plan to share individual participant data.
What supporting documents are/will be available?
No other documents available
Summary results
Have study results been published in a peer-reviewed journal?
No
Other publications
Have study results been made publicly available in another format?
No
Results – basic reporting
Results – plain English summary