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Trial registered on ANZCTR


Registration number
ACTRN12620000108910
Ethics application status
Approved
Date submitted
20/12/2019
Date registered
6/02/2020
Date last updated
19/11/2020
Date data sharing statement initially provided
6/02/2020
Date results information initially provided
18/06/2020
Type of registration
Prospectively registered

Titles & IDs
Public title
A First-in-Human Study of a new Controlled Release Formulation of Octreotide acetate in healthy male volunteers
Scientific title
A Phase I Study to evaluate the Pharmacokinetics and the Safety of a Controlled Release Formulation of Octreotide Acetate in Healthy Male Volunteers
Secondary ID [1] 299987 0
ASC-019O1V
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Acromegaly 315458 0
Neuroendocrine Tumours 315839 0
Condition category
Condition code
Metabolic and Endocrine 313757 313757 0 0
Other endocrine disorders
Cancer 314263 314263 0 0
Neuroendocrine tumour (NET)

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
15mg intramuscular injection of Octreotide CRF to be administered as a single dose in the upper gluteal area. Administration of injection will be performed by a trained nurse whilst subject is admitted to the Clinical Research Unit.
Intervention code [1] 316257 0
Treatment: Drugs
Comparator / control treatment
No control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 322168 0
To evaluate the safety and tolerability of Octreotide CRF after a single intramuscular administration at a dose of 15mg in young male volunteers.
The following assessments and tests will apply to assess outcome:
Physical Examination
Vital Signs
ECG's
Blood Sampling for Safety Assessment
Finger Stick Glucose Test
Timepoint [1] 322168 0
Complete physical examination: End of Study/Early Termination
Vital signs: Day 0 (1 and 6 hours post dose); Day 1; Day 2; Day 7; Day 14; Day 28 and End of Study/Early Termination (Day 42)
ECGs: Day 0 (1 and 6 hours post dose); Day 1; Day 2; Day 7; Day 14; Day 28 and End of Study/Early Termination (Day 42)
Blood samples for safety assessment: Day 1; Day 7; Day 21 and
Finger Stick Glucose Test: Day 0 (1 and 6 hours post dose); Day 1; Day 2 and Day 3
Primary outcome [2] 322169 0
To evaluate the pharmacokinetic (PK) profile of Octreotide CRF administered via intramuscular injection as a single dose of 15mg in young male volunteers. The following paraments to be examined:
• Maximum concentration (Cmax).
• Time of the maximum plasma drug concentration (Tmax).
• Area under the drug concentration-time curve, from time zero to the last measurable concentration (AUC0-t).
• Area under the drug concentration-time curve, from time zero to infinity (AUC0-inf).
• Area under the drug concentration-time curve, from time zero to Day 7 (AUC0-D7).
• Area under the drug concentration-time curve, from time zero to Day 14 (AUC0-D14).
• Area under the drug concentration-time curve, from time zero to Day 28 (AUC0-D28).
• Percent of AUC0-inf extrapolated (%AUC0-inf extrap).
• Apparent terminal half-life (t½).
• Apparent terminal elimination rate constant (Kel).
• Apparent total body clearance (CL/F).
• Apparent volume of distribution (Vd/F).
• Mean Residence Time (MRT).

Plasma samples will be sent for PK (Octreotide) analysis by LC-MS/MS
Timepoint [2] 322169 0
PK sampling: Day 0 (1 and 6 hour post dose); Day 1; Day 2; Day 3; Day 7; Day 10; Day 14; Day 21; Day 28; Day 35 and End of
Study/Early Termination (Day 42)
Secondary outcome [1] 377561 0
Composite secondary outcome to assess the incidence and severity of local reactions at the site of IM injection as collected via Visual Assessment Scale (VAS).
Timepoint [1] 377561 0
Visual Assessment Scale Self Assessment: Day 0 (0; 0.5; 1; 2; 3 and 6 hours post dose); Day 1; Day 2; Day 7; Day 14; Day 21 and End of Study/Early Termination (Day 42)
Secondary outcome [2] 377562 0
To assess the profile of the pharmacodynamic (PD) marker Insulin-like growth factor 1 (IGF 1) by means of serum assay following the administration of Octreotide CRF via intramuscular injection at a single dose of 15mg in young male volunteers. (Exploratory Outcome)
Timepoint [2] 377562 0
PD Sampling: Day 0 (1 and 6 hour post dose); Day 1; Day 2; Day 3; Day 7; Day 10; Day 14; Day 21; Day 28; Day 35 and End of Study/Early Termination (Day 42)

Eligibility
Key inclusion criteria
1. Healthy male subjects, aged 18-45 years (inclusive at the time of informed consent);
2. Participants must be in good general health, with no significant medical history, have no clinically significant abnormalities on physical examination at Screening and before administration of the initial dose of study drug;
3. Participants must have a minimum body weight of 50kg, and the BMI index (expressed as weight [kg] / height [m2]) must be between 19 and 29 at Screening.
4. Participants must have clinical laboratory values within normal range as specified by the testing laboratory, unless deemed not clinically significant by the Investigator;
5. Participants must have no relevant dietary restrictions, and be willing to consume standard meals provided during the confinement period;
6. Participants engaged in sexual relations with a woman of childbearing potential (WOCBP) must use an acceptable, highly effective, double-barrier contraceptive method from Screening until at least 90 days after dosing. Acceptable methods of contraception include the use of condoms and the use of an effective contraceptive for the female partner that include: oral contraceptive pills (OCPs), long-acting implantable hormones, injectable hormones, a vaginal ring or an intrauterine device (IUD). Participants with same sex partners (abstinence from penile-vaginal intercourse), participants who are surgically sterile (>30 days since vasectomy with no viable sperm), participants whose female partner is post-menopausal or abstinent participants are eligible when this is their preferred and usual lifestyle;
7. Participants must not donate sperm for at least 90 days after dosing with the study drug;
8. Participants must have the ability and willingness to attend the necessary visits to the Clinical Research Unit (CRU);
9. Clinically acceptable blood pressure and pulse rate in supine (systolic blood pressure -SBP- between 90-140 mm Hg/ diastolic blood pressure -DBP- between 50-95 mm Hg / heart rate -HR- between 50-100 bpm). Blood pressure and pulse will be measured after a minimum of 10 minutes of resting.
10. Able to understand the nature of the study and comply with all their requirements.
11. Participants must be willing and able to provide written informed consent after the nature of the study has been explained and prior to the commencement of any study procedures.
Minimum age
18 Years
Maximum age
45 Years
Gender
Males
Can healthy volunteers participate?
Yes
Key exclusion criteria
1. Known thyroid disease, even if effectively euthyroid because of treatment.
2. Known hypersensitivity to any component of the study drug;
3. Planning for the female partner to become pregnant at any time during the study, including the follow-up period;
4. Prior or ongoing medical conditions, medical history, physical findings, or laboratory abnormality that, in the Investigator’s opinion, could adversely affect the safety of the participant;
5. Presence of any underlying physical or psychological medical condition that, in the opinion of the Investigator, would make it unlikely that the participant will comply with the protocol or complete the study per protocol;
6. Background or clinical evidence of chronic diseases.
7. Any surgical or medical condition that could interfere with the absorption, distribution, metabolism, or excretion of the study drug, including impaired renal or hepatic function, diabetes mellitus, cardiovascular abnormalities, chronic symptoms of pronounced constipation or diarrhoea or conditions associated with total or partial obstruction of the urinary tract;
8. Having undergone any major surgery during the 6 months prior to the first study drug administration;
9. Blood donation or significant blood loss ( more or equal to 500mL within 60 days prior to the first study drug administration;
10. Plasma donation within 7 days prior to the first study drug administration;
11. Fever (body temperature more than 38°C) or symptomatic viral or bacterial infection within 2 weeks prior to Screening;
12. Any acute illness within 30 days prior to Day 0;
13. History of severe allergic or anaphylactic reactions;
14. Presence or history of allergies requiring acute or chronic treatment (except seasonal allergic rhinitis).
15. History of malignancy except for non-melanoma skin cancer excised more than 2 years prior to Screening;
16. Abnormal ECG findings at Screening including PR more or equal to 220 msec, QRS more ore equal to 120 msec, and Fridericia's correction more than 450 msec or ST wave changes or any other abnormal findings that are considered by the Investigator to be clinically significant,
17. History or presence of a condition associated with significant immunosuppression;
18. History of life-threatening infection (e.g. meningitis);
19. Infections requiring parenteral antibiotics within the 1 month prior to Screening;
20. Exposure to any significantly immune suppressing drug (including experimental therapies as part of a clinical trial) within the 4 months prior to Screening or 5-half-lives, whichever is longer;
21. Positive test for hepatitis C HCV virus antibody, hepatitis B surface antigen (HBsAg), or human immunodeficiency virus (HIV) antibody at Screening;
22. Participants with a positive urine drug screen test (including: cotinine, amphetamines, methamphetamines, phencyclidine, barbiturate, methadone, tricyclic antidepressant, cocaine, opiates, cannabinoids and benzodiazepines), and alcohol breath test;
23. Participants with a history of substance abuse or dependency or history of recreational intravenous (IV) drug use over the last 5 years (by self-declaration);
24. Regular alcohol consumption defined as more than 21 alcohol units per week (where 1 unit = 284 mL of beer, 25 mL of 40% spirit or a 125 mL glass of wine). Participant is unwilling to abstain from alcohol beginning 48 hours prior to admission to the CRU and during the confinement period;
25. Regular consumption of stimulating beverages containing xantine defined as > 5 coffees, teas or coca cola drinks/ day, or more than 3 energy drinks/week. Participant is unwilling to abstain from stimulating beverages consumption beginning 48 hours prior to admission to the CRU and during the confinement period;
26. Participants who used nicotine-based products (including smoking tobacco, smokeless tobacco, and nicotine patches) less than 6 months before informed consent.
27. Use of any IP or investigational medical device within 90 days prior to Screening, or 5 half-lives of the product (whichever is the longest) or participation in more than 4 investigational drug studies within 1 year prior to Screening;
28. Use of any prescription drugs, over the counter (OTC) medication, herbal remedies, supplements or vitamins within 14 days prior to dosing and during course of study without prior approval of the Investigator and Medical Monitor. Simple analgesia (paracetamol) may be permitted at the discretion of the Investigator;
29. Inability to refrain from consumption of grapefruit and Seville oranges or St. John’s Wort within 5 days prior to the first dose of study drug and until the final PK assessment;
30. Participant is unwilling to refrain from strenuous exercise (including weight-lifting) from 3 days prior to admission to the CRU until completion of the final Follow-up visit.

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
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 1
Type of endpoint(s)
Pharmacokinetics
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)
SA
Recruitment hospital [1] 15387 0
CMAX Clinical Research Pty Ltd - Adelaide
Recruitment postcode(s) [1] 28704 0
5000 - Adelaide

Funding & Sponsors
Funding source category [1] 304446 0
Commercial sector/Industry
Name [1] 304446 0
Ascil Australia Pty Ltd
Address [1] 304446 0
Cohort - health & knowledge precinct
16 Nexus Way
Southport
Queensland, 4215
Australia
Country [1] 304446 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
Ascil Australia Pty Ltd
Address
Cohort - health & knowledge precinct
16 Nexus Way
Southport
Queensland, 4215
Australia
Country
Australia
Secondary sponsor category [1] 304710 0
Commercial sector/Industry
Name [1] 304710 0
Clinical Network Services
Address [1] 304710 0
Level 2, 381 MacArthur Ave, Hamilton, Queensland, 4007, Australia
Country [1] 304710 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 304880 0
Bellberry Ethics
Ethics committee address [1] 304880 0
123 Glen Osmond Rd, Eastwood SA 5063
Ethics committee country [1] 304880 0
Australia
Date submitted for ethics approval [1] 304880 0
27/11/2019
Approval date [1] 304880 0
24/12/2019
Ethics approval number [1] 304880 0
2019-11-1037

Summary
Brief summary
This study will determine the pharmacokinetics and safety of the controlled released formulation of Octreotide acetate in healthy male volunteers

Who is it for?
You may be eligible to join this study if you are male, aged 18-45, and in good general health.

Study details
After a screening period beginning up to 28 days before admission to the Clinical Research Unit (CRU), all participants in this study will receive one injection of Octreotide acetate. As part of the study, participants will undergo safety assessments, pharmacokinetic, pharmacodynamic and global local tolerance assessment. Participants will be admitted to the CRU until day 2.
This new formulation of Octreotide will provide a significant reduction of the volume of administration and deliver an immediate onset of action. Additionally the long-acting release is intended to potentially result in less frequent dosing which could improve treatment compliance and quality of life in patients.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 98514 0
Dr Angela Molga
Address 98514 0
CMAX Clinical Research - Level 5, 18a North Terrace; Adelaide SA 5000
Country 98514 0
Australia
Phone 98514 0
+61 424 666 247
Fax 98514 0
Email 98514 0
Angela.Molga@sa.gov.au
Contact person for public queries
Name 98515 0
Ms Clinical Network Services
Address 98515 0
Clinical Network Services - Level 2, 381 MacArthur Ave, Hamilton, QLD, 4007, Australia
Country 98515 0
Australia
Phone 98515 0
+61 7 3719 6000
Fax 98515 0
Email 98515 0
cns@clinical.net.au
Contact person for scientific queries
Name 98516 0
A/Prof Angela Molga
Address 98516 0
CMAX Clinical Research - Level 5, 18a North Terrace; Adelaide SA 5000
Country 98516 0
Australia
Phone 98516 0
+61 424 666 247
Fax 98516 0
Email 98516 0
Angela.Molga@sa.gov.au

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 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?
Results – basic reporting
Results – plain English summary