Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12614000604606
Ethics application status
Approved
Date submitted
2/06/2014
Date registered
6/06/2014
Date last updated
4/12/2015
Type of registration
Prospectively registered

Titles & IDs
Public title
The safety and effectiveness of testosterone pellet implantation in hypogonadal males
Scientific title
An Open-Label Study to Characterize the Pharmacokinetics, Effectiveness, and Safety of Subcutaneous Implantation of 12 Testosterone Pellets (AA3000 75mg) in Hypogonadal Males
Secondary ID [1] 284683 0
Nil
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Hypogonadism 292023 0
Condition category
Condition code
Metabolic and Endocrine 292369 292369 0 0
Other metabolic disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
12 pellets each containing 75mg (total dose 900mg) of testosterone will be implanted under the skin of the side of the buttocks. The local area will be cleaned with antiseptic and local anesthetic injected. A small cut will be made and the testosterone pellets inserted under the skin using an applicator device called a trocar. Adhesive strips will be applied to close the insertion site and dressing to cover the area. The pellets remain in situ and dissolve over time. If a situation arises that necessitates discontinuation of testosterone, the pellets must be surgically removed.
Intervention code [1] 289468 0
Treatment: Drugs
Comparator / control treatment
Not applicable
Control group
Uncontrolled

Outcomes
Primary outcome [1] 292225 0
Primary Outcome 1: Study the pharmacokinetics of subcutaneous implantation of 12 testosterone pellets in hypogonadal males. This will be done by collecting samples and analysis of testosterone levels in the blood by a central laboratory.
Timepoint [1] 292225 0
Timepoint: Blood samples will be collected before implantation and 5, 8, 15, 29, 57, 85 and 113 days after implantation.
Primary outcome [2] 292226 0
Primary Outcome 2: Study the effectiveness of subcutaneous implantation of 12 testosterone pellets in hypogonadal males (with testosterone levels <300 ng/dL). This will be done by collection of information from questionnaires completed by the participants about erectile function, depression and androgen deficiency. The questionnaires to be used include: Center for Epidemiological Studies Depression (CES-D) Questionnaire; International Index of Erectile Function (IIEF); Quantitative Androgen Deficiency in the Aging Male (qADAM); and Subject Satisfaction with Treatment.
Timepoint [2] 292226 0
Timepoint: Questionnaires will be completed before implantation and 15, 29, 85 and 113 days after implantation.
Primary outcome [3] 292227 0
Primary Outcome 3: Study the safety of subcutaneous implantation of 12 testosterone pellets in hypogonadal males (with testosterone levels <300 ng/dL).
The most commonly reported adverse events include: implant site pain, swelling, inflammation, induraton, and erythema, discharge, haemorrhage, and haematoma; injection site pain and there is a risk of injection site infection, accidental expulsion of the pellets and a small skin scar at the implantation site. Adverse events associated with testosterone replacement therapy in general include: changes in sexual desire (increase or decrease) , headache, acne, nausea, itching, muscle pain, deepening of the voice, changes in skin colour, increased body hair, male pattern baldness or increased baldness, changes in liver function tests, hepatitis, rarely hepatocellular neoplasm, elevation of certain blood electrolytes, depression, nervousness, generalized parasthesia, mood alterations, increase in red blood cells, suppression of certain blood clotting factors, increase in cholesterol levels, as well as prolonged, frequent and painful erections. Increased and decreased blood pressure can also occur. There is a possible increased risk of prostate cancer.
Timepoint [3] 292227 0
This will be done by collection of information on adverse events and monitoring of laboratory safety results and vital signs from the time of implantation for 113 days.
Secondary outcome [1] 308461 0
nil
Timepoint [1] 308461 0
nil

Eligibility
Key inclusion criteria
1. Male
2. Serum testosterone level of less than 300ng/dL
3. Body mass index between 20 and 40
4. Be in good general health otherwise
5. Able to complete questionnaires
Minimum age
18 Years
Maximum age
70 Years
Sex
Males
Can healthy volunteers participate?
No
Key exclusion criteria
1. History of allergy or hypersensitivity to the study medication
2. History of alcoholism or substance abuse
3. History of chronic use of medications such as glucocorticoids
4. Previous use or planned use during the study of testosterone products (long acting depot products within 6 months, short acting injectables within 6 weeks, topical or oral products within 14 days before the screening visit)
5. Use of medications that may interfere with androgen metabolism (e.g. spironolactone, cimetidine, 5a-reductase inhibitors, hCG, androgen, estrogen, anabolic steroid, DHEA, or herbal hormone products) within 4 weeks of screening visit or plans to use these during the study.
6. History of myocardial infarction, unstable angina, heart failure including congestive heart failure, or ventricular dysrhythmia
7. History of venous thromboembolic disease (eg, deep vein thrombosis or pulmonary embolism).
8. Uncontrolled hypertension
9. Uncontrolled diabetes
10. Significant cerebrovascular disease
11. History of HIV
12. History of polycythemia or erythyrocytosis
13. Prostate cancer or a history of prostate cancer
14. Serum prostate specific antigen (PSA) level greater than or equal to 4 ng/mL
15. Breast cancer
16. Liver disease
17. Hyperparathyroidism
18. Received investigational drug within 30 days before screening 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 2
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
Pharmacokinetics - the measured concentration for testosterone will be graphed and tabled versus time. Summary statistics will be calculated and reported. Pharmacokinetic parameter values will be calculated and reported.
Effectiveness - change from baseline in overall satisfaction of erectile function, depression and androgen deficiency questionnaires will be summarised.
Safety – adverse events will be summarised. Change in pre-dose for each laboratory test and vital sign will be summarised descriptively at each time point collected.
Since this is primarily a pharmacokinetic study, no formal sample size calculation was required. The selection of approximately 24 subjects is typical for such studies.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
17/06/2014
Actual
11/07/2014
Date of last participant enrolment
Anticipated
30/09/2014
Actual
8/11/2014
Date of last data collection
Anticipated
Actual
Sample size
Target
24
Accrual to date
Final
15
Recruitment in Australia
Recruitment state(s)
NSW,VIC

Funding & Sponsors
Funding source category [1] 289303 0
Commercial sector/Industry
Name [1] 289303 0
Auxilium Pharmaceuticals, Inc.
Country [1] 289303 0
United States of America
Primary sponsor type
Commercial sector/Industry
Name
Auxilium Pharmaceuticals, Inc.
Address
640 Lee Road
Chesterbrook, PA 19087
Country
United States of America
Secondary sponsor category [1] 287973 0
None
Name [1] 287973 0
Address [1] 287973 0
Country [1] 287973 0
Other collaborator category [1] 277979 0
Commercial sector/Industry
Name [1] 277979 0
Novotech (Australia) Pty Limited
Address [1] 277979 0
Level 3, 235 Pyrmont Street, Pyrmont, NSW 2009
Country [1] 277979 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 291067 0
Bellberry Human Research Ethics Committee
Ethics committee address [1] 291067 0
129 Glen Osmond Road Eastwood South Australia 5063
Ethics committee country [1] 291067 0
Australia
Date submitted for ethics approval [1] 291067 0
02/04/2014
Approval date [1] 291067 0
29/05/2014
Ethics approval number [1] 291067 0

Summary
Brief summary
This trial aims to study the pharmacokinetics, effectiveness and safety of 12 pellets of 75mg testosterone (900mg total) implanted under the skin in males who have hypogonadism. Testosterone replacement therapy may help to restore male secondary characteristics, sexual behaviour, energy, mood and muscle development. This trial will enrol 24 male participants between the ages of 18-70 who have blood testosterone levels below 300ng/dL. All participants will undergo a screening visit 21 days prior to check for eligibility. Eligible participants will undergo an implantation procedure where 12 testosterone pellets will be implanted under the skin. Blood samples will be collected at various timepoints throughout the trial for pharmacokinetic analysis and safety parameters. Participants will also complete a series of questionnaires throughout the trial. Participants will be followed up for 113 days.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 48770 0
Dr Chris McMahon
Address 48770 0
Berry Road Medical Centre
Suites 2-4,
1A Berry Rd,
ST LEONARDS NSW 2065
Country 48770 0
Australia
Phone 48770 0
61 2 9437 3906
Fax 48770 0
61 2 9906 5900
Email 48770 0
[email protected]
Contact person for public queries
Name 48771 0
Ms Daphne Craw
Address 48771 0
Novotech (Australia) Pty Limited
4 Zigzag Street
Red Hill, QLD 4059
Country 48771 0
Australia
Phone 48771 0
+61 7 3137 6200
Fax 48771 0
+61 7 3137 6298
Email 48771 0
[email protected]
Contact person for scientific queries
Name 48772 0
Mr Nigel Jones
Address 48772 0
Auxilium Pharmaceuticals
Orchard Lea Winkfield Lane
Windsor SL4 4RU
Country 48772 0
United Kingdom
Phone 48772 0
+44 1443 421707
Fax 48772 0
+44 1344 887666
Email 48772 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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