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Trial registered on ANZCTR


Registration number
ACTRN12615000045516
Ethics application status
Approved
Date submitted
1/12/2014
Date registered
21/01/2015
Date last updated
5/09/2018
Type of registration
Prospectively registered

Titles & IDs
Public title
Pharmacokinetics of Testosterone Cream Applied to Scrotal Skin in healthy male volunteers
Scientific title
Pharmacokinetics of Testosterone Cream Applied to Scrotal Skin in healthy male volunteers
Secondary ID [1] 285749 0
Nil
Universal Trial Number (UTN)
Trial acronym
SSTCream
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Healthy male volunteers - dose finding - testosterone pharmacology 293636 0
Condition category
Condition code
Other 293944 293944 0 0
Research that is not of generic health relevance and not applicable to specific health categories listed above

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Healthy volunteers will visit the study centre 5 times.
2 separate injections of Nandrolone Decanoate will be given to temporarily suppress testosterone levels of healthy male volunteers. These healthy volunteers will be administered an intramuscular injection of 200mgs of Nandrolone Decanoate 3 days prior to and 100mgs 4 days after the first testosterone cream dose.
At the study centre, 3 doses (12.5mgs; 25mgs; 50mgs) of Testosterone Cream will be self-administered by healthy volunteers on 3 separate occasions to scrotal skin. 3 days after the first Nandrolone Decanoate injection the healthy volunteer will wear a disposable latex glove to self-administer the first random dose of testosterone cream. Blood samples will be taken every hour for 12 hours followed by second hourly for 4 hours. The healthy volunteer will then go home where he will collect a drop of blood onto blotting paper 24 hours after his dose of testosterone cream. This regime will be repeated for the 2 other random Testosterone Cream doses. There will be at least 2 days washout period between each subsequent dose of testosterone cream. The healthy volunteer will be at the study centre for approximately 16 hours of monitoring after each random dose of Testosterone Cream.
Intervention code [1] 290711 0
Treatment: Drugs
Comparator / control treatment
Internally controlled dose finding study
Control group
Dose comparison

Outcomes
Primary outcome [1] 293703 0
Pharmacokinetics of testosterone of 3 different, single dose applications to scrotal skin with serum testosterone measured by liquid chromatography mass spectrometry and pharmacokinetics parameters estimated by standard pharmacological analysis - Tmax, Cmax and Area Under the Curve
Timepoint [1] 293703 0
24 hour sampling
venous bloods at -15, -5 minutes; random testosterone dose applied; venous bloods continue at 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 14, 16 hours plus venous blood spot at 0, 4, 8, 12, 16 hours and at 24 hours by finger-prick
Secondary outcome [1] 311635 0
Serum Nandrolone measured by mass spectrometry
Timepoint [1] 311635 0
24 hour sampling
venous bloods at -15, -5 minutes; random testosterone dose applied; venous bloods continue at 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 14, 16 hours plus venous blood spot at 0, 4, 8, 12, 16 hours and at 24 hours by finger-prick
Secondary outcome [2] 311965 0
Dihydrotestosterone (DHT) levels measured by mass spectrometry
Timepoint [2] 311965 0
24 hour sampling
venous bloods at -15, -5 minutes; random testosterone dose applied; venous bloods continue at 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 14, 16 hours plus venous blood spot at 0, 4, 8, 12, 16 hours and at 24 hours by finger-prick
Secondary outcome [3] 311966 0
Estradiol (E2) levels measured by mass spectrometry
Timepoint [3] 311966 0
24 hour sampling
venous bloods at -15, -5 minutes; random testosterone dose applied; venous bloods continue at 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 14, 16 hours plus venous blood spot at 0, 4, 8, 12, 16 hours and at 24 hours by finger-prick
Secondary outcome [4] 311967 0
Tolerability of cream applied to scrotal skin assessed using 5 point Likert Scale
Timepoint [4] 311967 0
5 point Likert Scale will be used to assess tolerability at 24 hours post application of each random testosterone dose.

Eligibility
Key inclusion criteria
Healthy male volunteers aged greater than or equal to 18 years of age to less than or equal to 50 years of age
Able to personally read and understand the study Participant Information and Consent Form and provide written, signed and dated informed consent to participate in study.
Able to comply with all study procedures and visits
Minimum age
18 Years
Maximum age
50 Years
Gender
Males
Can healthy volunteers participate?
Yes
Key exclusion criteria
No serious chronic medical illness requiring regular prescribed medication.
No contraindications to testosterone including prostate or breast cancer, untreated sleep apnoea or polycythaemia.
No history of major psychiatric disease or psychological condition that may limit understanding and compliance with study requirements.
No regular use of medications that interfere with dermal absorption or metabolism of testosterone.

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)
Sealed opaque envelopes
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Computer generated randomisation list
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Crossover
Other design features
Dose finding
Phase
Phase 4
Type of endpoint(s)
Pharmacokinetics
Statistical methods / analysis
Cross-over study analysis with dose as covariate by standard sample size for a standard crossover bioavailability study. If no significant effects are confirmed with this powerful design the differences are clinically insignificant

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)
NSW
Recruitment hospital [1] 3216 0
Concord Repatriation Hospital - Concord
Recruitment postcode(s) [1] 8994 0
2139 - Concord Repatriation Hospital

Funding & Sponsors
Funding source category [1] 290319 0
Commercial sector/Industry
Name [1] 290319 0
Lawley Pharmaceuticals Pty Ltd
Address [1] 290319 0
Unit 2/ 15A Harrogate Street
WEST LEEDERVILLE, WA, 6007
Country [1] 290319 0
Australia
Primary sponsor type
Hospital
Name
Andrology Department, Concord Hospital
Address
Building 22
Concord Repatriation General Hospital
Hospital Road
CONCORD NSW 2139
Country
Australia
Secondary sponsor category [1] 289036 0
None
Name [1] 289036 0
Address [1] 289036 0
Country [1] 289036 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 292026 0
Sydney Local Health District - CRGH (EC00118)
Ethics committee address [1] 292026 0
Concord Repatriation General Hospital
Hospital Road
CONCORD NSW 2139
Ethics committee country [1] 292026 0
Australia
Date submitted for ethics approval [1] 292026 0
18/11/2014
Approval date [1] 292026 0
09/03/2015
Ethics approval number [1] 292026 0
HREC/14/CRGH/267

Summary
Brief summary
The Pharmacokinetics of Testosterone Cream Applied to Scrotal Skin study is a dose finding study to determine the effectiveness of absorption of testosterone cream when applied in an alternative way to current practice.

Long-term compliance with testosterone replacement therapy requires convenience in the delivery system to facilitate continuation of treatment with minimal intrusion or disruption to daily life. Current product information for transdermal( via the skin) application of testosterone states it is not to be administered to the genital area.
Transdermal application of testosterone depends on the stratum corneum, the layers of dead skin cells which limit permeability of small molecules through the skin. Skin varies widely in thickness and steroidal (cortisol) permeability. The thinnest stratum corneum and highest steroidal permeability is scrotal skin. The study will determine the absorption rate of testosterone cream when applied to scrotal skin.

The study will be conducted at the Department of Andrology, CRGH and will aim to recruit 12 healthy male volunteers from the local community.

Eligible and consenting participants will visit the study centre 5 times. The men will receive 2 separate intramuscular injection of nandrolone decanoate to temporarily suppress testosterone levels. They will self-administer 3 dose applications (in random order) of testosterone cream to their scrotal skin. Venous and capillary dried blood spots will be collected before and over a 24 hour period before and after application of the cream to monitor hormone levels.
Trial website
Trial related presentations / publications
R. Iyer, S. F. Mok, S. Savkovic, L.Turner, G. Fraser, R. Desai, V. Jayadev, A. J. Conway and D. Handelsman (2017) Pharmacokinetics of testosterone cream applied to scrotal skin. Andrology 2017, 5, 725-731
Public notes

Contacts
Principal investigator
Name 53106 0
Prof David Handelsman
Address 53106 0
Department of Andrology
Building 22
Concord Repatriation General Hospital
Hospital Road
CONCORD NSW 2139
Country 53106 0
Australia
Phone 53106 0
+61 2 97677222
Fax 53106 0
Email 53106 0
djh@anzac.edu.au
Contact person for public queries
Name 53107 0
Prof David Handelsman
Address 53107 0
Department of Andrology
Building 22
Concord Repatriation General Hospital
Hospital Road
CONCORD NSW 2139
Country 53107 0
Australia
Phone 53107 0
+61 2 97677222
Fax 53107 0
Email 53107 0
djh@anzac.edu.au
Contact person for scientific queries
Name 53108 0
Prof David Handelsman
Address 53108 0
Department of Andrology
Building 22
Concord Repatriation General Hospital
Hospital Road
CONCORD NSW 2139
Country 53108 0
Australia
Phone 53108 0
+61 2 97677222
Fax 53108 0
Email 53108 0
djh@anzac.edu.au

No information has been provided regarding IPD availability
Summary results
Have study results been published in a peer-reviewed journal?
Other publications
Have study results been made publicly available in another format?
Results – basic reporting
Results – plain English summary