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Trial registered on ANZCTR


Registration number
ACTRN12620001261909
Ethics application status
Approved
Date submitted
30/09/2020
Date registered
24/11/2020
Date last updated
19/05/2021
Date data sharing statement initially provided
24/11/2020
Type of registration
Prospectively registered

Titles & IDs
Public title
A First-in-Human Study of a Controlled Release Formulation of Lanreotide acetate in healthy male volunteers
Scientific title
A Phase I Study to evaluate the Pharmacokinetics and the Safety of a Controlled Release Formulation of Lanreotide acetate in Healthy Male Volunteers
Secondary ID [1] 302359 0
ASC-02001V
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Acromegaly 319136 0
Neuroendocrine Tumours 319137 0
Condition category
Condition code
Metabolic and Endocrine 317100 317100 0 0
Other endocrine disorders
Cancer 317101 317101 0 0
Neuroendocrine tumour (NET)

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
60mg or 120mg deep subcutaneous injection of Lanreotide CRF to be administered as a single dose in the superior external quadrant of the buttock or in the upper outer thigh. Administration of injection will be performed by a trained nurse whilst subject is admitted to the Clinical Research Unit.

2 cohorts of 8 participants each will be enrolled sequentially. Participants in cohort 1 will receive 60mg Lanreotide CRF and participants in cohort 2 will receive 120 mg Lanreotide CRF.
Strategies used to monitor adherence to the intervention: Laboratory tests and IP accountability review during monitoring visits
Intervention code [1] 318648 0
Treatment: Drugs
Comparator / control treatment
no control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 325185 0
To evaluate the safety and tolerability of Lanreotide CRF after a single deep subcutaneous administration at doses of 60mg or 120mg 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
It is a composite outcome.

Vital signs and blood safety tests: systolic and diastolic blood pressure, pulse rate, body temperature, respiratory rate, blood chemistry and thyroid function test.
Type of ECG: 12- Lead ECGs
Timepoint [1] 325185 0
Complete physical examination
Vital signs: Day 0 (1 and 6 hours post dose); Day 1; Day 2; Day 7; Day 14; Day 28; Day 35; Day 42; Day 49 Day and End of Study/Early Termination (Day 56)
ECGs: Day 0 (1 and 6 hours post dose); Day 1; Day 2; Day 7; Day 14; Day 28; Day 42 and End of Study/Early Termination (Day 56)
Blood samples for safety assessment: Day 1; Day 7; Day 21; Day 42 and End of Study/Early Termination (Day 56)
Finger Stick Glucose Test: Day 0 (1 and 6 hours post dose); Day 1; Day 2 and Day 3
Primary outcome [2] 325186 0
To evaluate the pharmacokinetic (PK) profile of Lanreotide CRF administered via deep subcutaneous injection as a single dose of 60mg or 120mg in young male volunteers. The following parameters 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).
• Area under the drug concentration-time curve, from time zero to Day 42 (AUC0-D42).
• Area under the drug concentration-time curve, from time zero to Day 49 (AUC0-D49).
• 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).
It is a composite Outcome

Plasma/Serum samples will be used to assess this outcome.
Timepoint [2] 325186 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; Day 42; Day 49 and End of Study/Early Termination (Day 56)
Secondary outcome [1] 387109 0
Composite secondary outcome to assess the incidence and severity of local reactions at the site of deep SC injection as collected via Visual Assessment Scale (VAS).
Timepoint [1] 387109 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; Day 42 and End of Study/Early Termination (Day 56)

Eligibility
Key inclusion criteria
1. Healthy male subjects, aged 18-50 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 (inclusive) 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, as per their normal dietary requirements;
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 (greater than 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
50 Years
Sex
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 followup 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 equals to 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 greater than 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 1 month before informed consent.
27. Use of any IP or investigational medical device within 40 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
Parallel
Other design features
Phase
Phase 1
Type of endpoint/s
Pharmacokinetics
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
19/12/2020
Actual
8/01/2021
Date of last participant enrolment
Anticipated
18/06/2021
Actual
Date of last data collection
Anticipated
27/08/2021
Actual
Sample size
Target
16
Accrual to date
2
Final
Recruitment in Australia
Recruitment state(s)
SA
Recruitment hospital [1] 17589 0
CMAX Clinical Research Pty Ltd - Adelaide
Recruitment postcode(s) [1] 31333 0
5000 - Adelaide

Funding & Sponsors
Funding source category [1] 306790 0
Commercial sector/Industry
Name [1] 306790 0
Ascil Australia Pty LTD
Country [1] 306790 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
Ascil Australia Pty LTD
Address
16 Nexus Way
Southport
Queensland, 4215
Australia
Country
Australia
Secondary sponsor category [1] 307340 0
None
Name [1] 307340 0
Address [1] 307340 0
Country [1] 307340 0
Other collaborator category [1] 281546 0
Commercial sector/Industry
Name [1] 281546 0
Novotech (Australia) Pty Limited
Address [1] 281546 0
Level 3, 235 Pyrmont Street, Pyrmont NSW 2009
Country [1] 281546 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 307030 0
Bellberry Limited HREC
Ethics committee address [1] 307030 0
123 Glen Osmond Road, Eastwood, SA 5063
Ethics committee country [1] 307030 0
Australia
Date submitted for ethics approval [1] 307030 0
18/11/2020
Approval date [1] 307030 0
22/12/2020
Ethics approval number [1] 307030 0
2020-10-1010

Summary
Brief summary
This study will determine the pharmacokinetics and safety of the controlled released formulation of Lanreotide acetate in healthy male volunteers
Who is it for?
You may be eligible to join this study if you are male, aged 18-50, and in good general health.
Study details
After a screening period beginning up to 28 days before admission to the Clinical Research Unit (CRU), 8 participants in this study will receive one injection of Lanreotide acetate at a dose of 60mg. In the absence of safety issues, the remaining 8 participants will receive one injection of Lanreotide acetate at a dose of 120mg. As part of the study, participants will undergo safety assessments, Plasma/serum pharmacokinetic and global local tolerance assessment. Participants will be admitted to the CRU until day 2. Compared to the product already available on the market, this new lanreotide formulation [Lanreotide CRF] allows for a more convenient administration for both the patients and caregivers.
The Lanreotide CRF is provided in a shorter and standard pre-filled syringe and a smaller needle is used for the injection (21G needle).
In terms of PK profile, an equivalent performance is expected for the new Lanreotide CRF formulation when compared to the marketed product.

It is hoped this research will determine whether this new lanreotide formulation can be administered safely without causing severe reactions. Once the PK profiles and safety have been determined in healthy volunteers, additional trials investigating the efficacy of Lanreotide CRF as a treatment for patients with neuroendocrine cancer or acromegaly may proceed.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 44502 0
Dr Jessica Gehlert
Address 44502 0
CMAX Clinical Research - Level 5, 18a North Terrace; Adelaide SA 5000
Country 44502 0
Australia
Phone 44502 0
+61 421311443
Fax 44502 0
Email 44502 0
[email protected]
Contact person for public queries
Name 44503 0
Dr Jessica Gehlert
Address 44503 0
CMAX Clinical Research - Level 5, 18a North Terrace; Adelaide SA 5000
Country 44503 0
Australia
Phone 44503 0
+61 421311443
Fax 44503 0
Email 44503 0
[email protected]
Contact person for scientific queries
Name 44504 0
Dr Jessica Gehlert
Address 44504 0
CMAX Clinical Research - Level 5, 18a North Terrace; Adelaide SA 5000
Country 44504 0
Australia
Phone 44504 0
+61 421311443
Fax 44504 0
Email 44504 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
None


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.