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Trial registered on ANZCTR


Registration number
ACTRN12611000854932
Ethics application status
Approved
Date submitted
9/08/2011
Date registered
11/08/2011
Date last updated
22/06/2012
Type of registration
Retrospectively registered

Titles & IDs
Public title
A Randomised, Placebo Controlled, Double-Blind, Single Ascending Dose and Multiple Dose Study to Assess the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Subcutaneous Doses of ATL1103 in Healthy Adult Male Subjects
Scientific title
A Randomised, Placebo Controlled, Double-Blind, Single Ascending Dose and Multiple Dose Study to Assess the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Subcutaneous Doses of ATL1103 in Healthy Adult Male Subjects
Secondary ID [1] 262799 0
Nil
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
ATL1103 is being developed as a potential treatment for diseases of excessive growth hormone and insulin-like growth hormone (IGF)-I action, including the condition acromegaly. 270506 0
Condition category
Condition code
Metabolic and Endocrine 270605 270605 0 0
Other metabolic disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Subjects will receive ATL1103 (growth hormone (GH) receptor antisense oligonucleotide) as a sterile aqueous solution administered by subcutaneous injection.

Stage A is a single asending dose study. Each subject receives only one dose level once during the study. The safety data from each cohort is reviewed before dosing of the next cohort. The dose of ATL1103 administrered is 25 mg for cohort 1, 75 mg for cohort 2, 250 mg for cohort 3 and 400 mg for cohort 4.
For Stage B, six doses of ATL1103 will be administered on days 1, 3, 5, 7, 14 and 21 of the study. The time between stages, and the dose per injection for stage B, is to be decided on review of the safety data from Stage A. For Stage B, subjects will be monitored for a further two weeks after the completion of dosing.
Intervention code [1] 267089 0
Treatment: Drugs
Comparator / control treatment
The placebo is an aqueous buffered saline solution colour-matched for ATL1103. The placebo will be administered by a single subcutaneous injection in stage A, and on days 1, 3, 5, 7, 14 and 21 in stage B.
Control group
Placebo

Outcomes
Primary outcome [1] 269063 0
A primary objective of the study is to evaluate the safety and tolerability of a single and multiple subcutaneous doses of ATL1103 when administered to healthy adult male volunteers. Safety and tolerability will be assessed by serum chemistry, haematology, urinalysis, physical exam, vital signs and electrocardiogram.
Timepoint [1] 269063 0
For Stage A: Subjects will receive the dose of ATL1103 and remain in the unit for 24 hours. There are three follow up visits on days 3, 4 and 7.

For Stage B: Subjects will be confined in the unit for seven days then return for seven out-patient visits up to Day 35.
Primary outcome [2] 269064 0
Single and multiple dose pharmacokinetic parameters including concentration-time profile of ATL1103.
Timepoint [2] 269064 0
Plasma and urine will be collected for ATL1103 assays at various timepoints pre- and post-dose.

Stage A
Plasma will be collected pre-dose, and for 10 timepoints in the 24 hours after administration of ATL1103, and again on days 3, 4 and 7. Urine will be collected for 24 hours after the administration of ATL1103.

Stage B
Plasma will be collected pre-dose, then at 11 timepoints in the 48 hours after administration of ATL1103 on days 1 and 21. Samples will also be collected on days 3, 5, 7, 14, 28 and 35. Urine will be collected for 24 hours after the first dose of ATL1103, and again on days 7 and 21.
Secondary outcome [1] 276893 0
Investigation of the pharmacodynamic effect of ATL1103 will be assessed by measurement of serum insulin-like growth factor (IGF)-I levels.
Timepoint [1] 276893 0
Serum will be collected for IGF-I assay four times in the first week, then weekly to Day 35 of the study.

Eligibility
Key inclusion criteria
1. Aged from 18 years up to 45 years (inclusive).
2. Male
3. Body Mass Index (BMI) BMI of 19 to 30 kg/m2 with body weight of between 70kg and 90kg.
4. Healthy as determined by a medical history
5. Serum IGF-1 levels within the normal range
6. Adequate venous access
7. Fluent in the English language.
8. Written informed consent.
Minimum age
18 Years
Maximum age
45 Years
Sex
Males
Can healthy volunteers participate?
Yes
Key exclusion criteria
Volunteers with any of the following criteria will not be eligible for participation in this study:
1. Hypersensitivity. History of allergy and/or hypersensitivity to any of the stated ingredients of the formulations. A known hypersensitivity to lidocaine or all surgical dressings which may be used in the study procedures.
2. Medical Conditions
a) History of clinically significant gastrointestinal, hepatic, renal, cardiovascular, dermatological, immunological, respiratory, endocrine, oncological, neurological, metabolic, psychiatric disease or haematological disorders.
b) Any history of clinically significant cardiac arrhythmias or the presence of clinically significant abnormalities on ECG at Screening.
c) Any evidence or history of hypotension or hypertension in the opinion of the PI following repeat assessment.
d) Any history of asthma during the last 10 years.
e) A calculated creatinine clearance of less than 75 mL/min.
f) Any predisposing condition that in the opinion of the Investigator might interfere with the absorption, distribution, metabolism and/or excretion of drugs.
g) History of abnormal bleeding tendencies or thrombophlebitis unrelated to venepuncture or intravenous cannulation, or a history of Hepatitis B, a positive test for Hepatitis B surface antigen, a history of Hepatitis C, a positive test for Hepatitis C antibody, a history of HIV infection or demonstration of HIV antibodies.
h) Inability to tolerate repeated venepuncture.
3. Laboratory Status. Any evidence of organ dysfunction, or any deviation in clinical laboratory values which is confirmed upon re-examination to be clinically significant (i.e., in the opinion of the PI would jeopardise the safety of the subject or impact on the validity of the study results), including a liver function test (LFT) > upper limit of normal (ULN). Total bilirubin levels > 1.5 x ULN will be allowed if associated with Gilbert’s syndrome.
4. Ethanol Use. Regular drinkers of more than four (4) units of alcohol daily (1 unit = 300 mL beer, 1 glass wine, 1 measure spirit) or those who may have difficulty abstaining from alcohol during the 48 hours prior to dose administration and until completion of blood sampling on Day 2 for the single-dose cohorts (Stage A) or Day 7 for the multiple-dose cohorts (Stage B).
5. Drug and Alcohol Abuse. History of, or current evidence of, abuse of alcohol or any drug substance, licit or illicit, or positive urine drug and alcohol screen for drugs of abuse and alcohol.
6. Smoking. Current smoker of not more than 5 cigarettes or equivalent per day prior to commencing the study, unable to completely stop smoking during the study.
7. Medication
a) Difficulty in abstaining from any prescription medications for 14 days prior to dose administration and for the duration of the study.
b) Difficulty in abstaining from over-the-counter (OTC) medications or herbal supplements for seven days prior to dose administration and for the duration of the study.
8. Administration site. Any tattoos in the anterior abdominal area which, in the opinion of the Investigator would preclude accurate local tolerance assessments of injection sites.
9. Xanthine Use. Difficulty in abstaining from food and/or beverages that contain caffeine or other xanthines
(e.g., coffee, tea, cola and chocolate) during the 24 hours prior to dose administration and whilst confined at the clinical facility.
10. Psychiatric or Psychological Disorder. History of any psychiatric illness or psychological disorder which may impair the ability to provide written informed consent or participate in the study.
11. Protocol Compliance. Poor compliers or those unlikely to attend the Unit.
12. Recent Study Participation. Receipt of any drug as part of a research study within 30 days of initial dose administration in this study.
13. Blood Donation. Standard blood donation (usually 550 mL) within the 12-week period before dose administration.
14. Dietary Habits. Unusual dietary habits, including vegetarian diets and excessive or unusual vitamin intakes.

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)
A randomisation schedule will be generated by a statistician using a computer program.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?



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

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
28/06/2011
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
36
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)

Funding & Sponsors
Funding source category [1] 267327 0
Commercial sector/Industry
Name [1] 267327 0
Antisense Therapeutics Limited
Country [1] 267327 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
Antisense Therapeutics Limited
Address
6 Wallace Avenue
Toorak Vic 3142
Country
Australia
Secondary sponsor category [1] 266595 0
None
Name [1] 266595 0
Address [1] 266595 0
Country [1] 266595 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 269313 0
Austin Health Human Research Ethics Committee
Ethics committee address [1] 269313 0
Henry Buck Building
Austin Hospital
145 Studley Road
HEIDELBERG VIC 3084
Ethics committee country [1] 269313 0
Australia
Date submitted for ethics approval [1] 269313 0
21/04/2011
Approval date [1] 269313 0
08/06/2011
Ethics approval number [1] 269313 0
H2011/04315

Summary
Brief summary
ATL1103 is being developed as a potential treatment for diseases of excessive growth hormone and insulin-like growth hormone (IGF-I) action. This is the first in man study for ATL1103, and is being conducted as a randomized, placebo-controlled, double-blind trial. Thirty six healthy male subjects will participate in the study. In stage A, subjects will receive one dose of either placebo or ATL1103 (at a dose of 25 mg, 75 mg, 250 mg or 400 mg). In stage B, subjects will receive 6 doses of placebo or ATL1103 (at a dose to be determined after review of the safety data from Stage A). All treatments will be administered by subcutaneous injection.
The primary objectives of the study is to evaluate the safety and tolerability of single or multiple injections of ATL1103, and to investigate the pharmacokinetic profiles of ATL1103 after subcutaneous administration. The effect of ATL1103 on serum IGF-I levels will also be monitored.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 32801 0
Address 32801 0
Country 32801 0
Phone 32801 0
Fax 32801 0
Email 32801 0
Contact person for public queries
Name 16048 0
Sue Turner
Address 16048 0
6 Wallace Avenue
Toorak VIC 3142
Country 16048 0
Australia
Phone 16048 0
+61 3 9827 8999
Fax 16048 0
+61 3 98271166
Email 16048 0
[email protected]
Contact person for scientific queries
Name 6976 0
Lynne Atley
Address 6976 0
6 Wallace Avenue
Toorak VIC 3142
Country 6976 0
Australia
Phone 6976 0
+61 3 9827 8999
Fax 6976 0
+61 3 98271166
Email 6976 0
[email protected]

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

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