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Trial registered on ANZCTR


Registration number
ACTRN12610000834055
Ethics application status
Approved
Date submitted
20/09/2010
Date registered
6/10/2010
Date last updated
11/09/2012
Type of registration
Prospectively registered

Titles & IDs
Public title
Bioequivalence study comparing AndroForte 5 (Registered Trademark (R)) and Testogel (R) 1%
Scientific title
An open-label, phase 2, single centre, randomised, crossover design bioequivalence study of AndroForte (R) 5 Compared With Testogel (R) 1% in Hypogonadal Men
Secondary ID [1] 252453 0
none
Universal Trial Number (UTN)
U1111-1116-5976
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Testosterone replacement therapy 257965 0
Hypogonadism 258217 0
Condition category
Condition code
Metabolic and Endocrine 258133 258133 0 0
Normal metabolism and endocrine development and function

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
AndroForte 5
white oil-in-water cream containing testosterone 50mg/mL
2ml of cream to be topically applied to torso once daily for 30 days.
Washout period 7 - 10 days between crossover treatments
Intervention code [1] 257019 0
Treatment: Drugs
Comparator / control treatment
Testogel 1% is testosterone dissolved in a hydroalcoholic solution.
Each sachet contains 50mg of testosterone (in 5g gel).
The contents of one sachet to be topically applied to torso once daily for 30 days.
Washout period 7 - 10 days between crossover treatments.
Control group
Active

Outcomes
Primary outcome [1] 258997 0
To assess Pharmacokinetic (PK) variables: Area under the curve (AUC), Average concentration (Cavg), Maximum plasma concentration (Cmax), Time to maximum plasma concentration (Tmax), % Fluctuation (with and without baseline correction) for AndroForte 5 and Testogel 1% on Day 1 and Day 30 by measuring serum testosterone & dihydrotestosterone.
Timepoint [1] 258997 0
PK serial sampling will be performed at -15 , -5, 0 min prior and 2, 4, 5, 6, 7, 8, 9, 10, 12, 16 and 24 hours post administration on Day 1 and 30 of Period I and II of each treatment
Secondary outcome [1] 265208 0
To determine the bioavailability of AndroForte 5 as compared to Testogel 1%, by measuring serum testosterone levels.
Timepoint [1] 265208 0
PK serial sampling will be performed at -15 , -5, 0 min prior and 2, 4, 5, 6, 7, 8, 9, 10, 12, 16 and 24 hours post administration on Day 1 and 30 of Period I and II of each treatment
Secondary outcome [2] 265817 0
To determine the proportion of samples within percentage testosterone target (% T) or outside target blood testosterone range. Percentage above testosterone [%AT], percentage below testosterone [%BT], by measuring serum testosterone levels.
Timepoint [2] 265817 0
PK serial sampling will be performed at -15 , -5, 0 min prior and 2, 4, 5, 6, 7, 8, 9, 10, 12, 16 and 24 hours post administration on Day 1 and 30 of Period I and II of each treatment
Secondary outcome [3] 265818 0
To compare the profiles of other reproductive hormones :- changes in blood dihydrotestosterone (DHT), estradiol (E2) and Sex Hormone Binding Globulin (SHBG). Suppression of blood Lutenising Hormone (LH) & Follicile Stimulating Hormone (FSH), by measuring reproductive hormone levels throughout the study.
Timepoint [3] 265818 0
after Day 1, Day 15 and Day 30 of each treatment period
Secondary outcome [4] 265819 0
To assess the safety and tolerability of AndroForte 5. Safety biochemistry and haematology blood samples will be collected & adverse events will recorded throughout the study.

The most common side effects experienced in 10% of subjects treated with Testogel (R) 1% and AndroForte (R) 5 are:
* Skin reactions at the application site - e.g. irritation, redness, dry or stinging skin
* Acne
Less common side effects, occurring between 1-10% of subjects treated include:
Headaches, dizziness, nausea, retention of salt and water, loss of head hair, increased body hair, changes in your mood & deepening of the voice
Timepoint [4] 265819 0
after Day 1, Day 15 and Day 30 of each treatment period.
Secondary outcome [5] 265820 0
Quality of Life (SF-36) and Mood, sexual function (Sexual Desire Inventory (SDI), International Index of Erectile Function (IIEF) assessment. Participants will complete these questionnaires throughout the study.
Timepoint [5] 265820 0
at Day 1 and Day 30 of each treatment period

Eligibility
Key inclusion criteria
Established androgen deficiency (primary or secondary) (including newly diagnosed persons) requiring androgen replacement therapy as determined by current Pharmaceutical Benefit Scheme (PBS) guidelines (laboratory results demonstrating that Australian guidelines have been met must be available for review)
Or
Established androgen deficiency (primary or secondary) and currently receiving androgen replacement therapy (at an equivalent dose as outlined in this protocol) and willing to withdraw from current androgen replacement therapy and observe the necessary washout period prior to entering the study as outlined below:

- 7 days for transdermal testosterone or oral testosterone undecanoate
- 6-12 weeks for intramuscular injections of testosterone esters
- 6 months since last dose for subcutaneous testosterone pellets or testosterone undecanoate
Minimum age
18 Years
Maximum age
75 Years
Gender
Males
Can healthy volunteers participate?
No
Key exclusion criteria
* Untreated obstructive sleep apnoea as determined by the Berlin Sleep Apnoea questionnaire

* Clinically significant non-malignant disease including, active clinically significant infection (requiring systemic antibiotics), cerebrovascular event or transient ischemic attack within 12 months prior to randomisation or major surgery within 3 months of randomisation


* Active cardiac disease defined as one or more of the following
- New York Heart Association functional classification of heart failure of greater than or equal to 2 or symptomatic angina
- Uncontrolled arrhythmias, or arrhythmias deemed clinically significant by the investigator
- Myocardial infarction, cardiac stenting or angioplasty in past 6 months

* Prior history of prostate cancer or other malignancy, which could affect compliance with the protocol or interpretation of study results. Cancer(s) treated with curative intent (including non-melanoma skin cancer) are eligible if disease-free for at least 2 years.

* Any form of respiratory failure requiring oxygen supplementation


* Evidence of a significant medical illness, abnormal laboratory finding or adverse event from prior androgen replacement therapy that would, in the investigators’ judgment, make the participant inappropriate for this study

* Receipt of therapy with another investigational drug within 4 weeks of Day 1 or current enrolment in another clinical trial


* Current smoker or past smoker who has ceased smoking within the past year

* Elevated blood pressure (greater than or equal to 140/90mmHg) at screening or a diagnosis of hypertension unless on stable therapy for at least 3 months and currently normotensive


* History of mental illness (requiring ongoing psychotropic medications)

* Active substance abuse


* Known to be human immunodeficiency virus (HIV) or hepatitis B surface antigen positive

* Planned elective surgery within 1 month of randomisation or during the study period


* Generalised skin disease on the abdomen that may be affected by or affect testosterone absorption at the site of transdermal absorption – e.g. psoriasis

* Body Mass Index (BMI) of less than 18 kg/m2 or more than 35 kg/m2 as either extreme may result in hypogonadism responsive to normalisation of weight


* Currently on medications, herbal remedies or vitamins/juices (e.g. grapefruit juice) known to
- Be strong inducers/ inhibitors of Cytochrome 3A4 (CYP 3A4)
- Affect the production (e.g. opiates, gonadotropin releasing hormone (GnRH) agonists) or action (e.g. spironolactone) of androgens
- Affect the production of SHBG (e.g. thyroxine, insulin, growth hormone, antiepileptics), unless the dose has been stable for at least 3 months and will remain so.

* Dementia or altered cognitive function that would interfere with the participant’s safety or compliance to the study procedures

* Use of topical salves or topical steroids to abdomen within past 7 days


* Participants unwilling to adhere to the guidelines in regard to intimate contact post application

* Known allergy to almonds


* Participants experiencing severe voiding symptoms as identified on the International Prostate Symptom Score (IPSS) questionnaire

* Men who are able to father a child who are unwilling to use an acceptable method of contraception during the trial

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)
This is an open study & eligible participants will be randomly assigned the order in which they will receive the 2 treatment options prior to crossing over to the other treatment period. The hospital pharmacist will hold the allocation schedule & dispense according to this schedule.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
centrally randomisation by computer
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Crossover
Other design features
N/A
Phase
Phase 2
Type of endpoint(s)
Bio-equivalence
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)

Funding & Sponsors
Funding source category [1] 257478 0
Commercial sector/Industry
Name [1] 257478 0
Lawley Pharmaceuticals
Address [1] 257478 0
Unit 2, 15a Harrogate Street
West Leederville
Perth
Western Australia
6007
Country [1] 257478 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
Lawley Pharmaceuticals
Address
Lawley Phrmaceuticals
Unit 2, 15a Harrogate Street
West Leederville
Perth
Western Australia
6007
Country
Australia
Secondary sponsor category [1] 256999 0
None
Name [1] 256999 0
Address [1] 256999 0
Country [1] 256999 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 259506 0
Royal Adelaide Hospital Human Research Ethics Committee (HREC)
Ethics committee address [1] 259506 0
Human Research Ethics Committee
Royal Adelaide Hospital
North Terrace
Adelaide
SA 5000
Ethics committee country [1] 259506 0
Australia
Date submitted for ethics approval [1] 259506 0
18/08/2010
Approval date [1] 259506 0
17/09/2010
Ethics approval number [1] 259506 0

Summary
Brief summary
The study will determine if AndroForte (R) 5 (testosterone cream) is bioequivalent to Testogel (R) 1% (testosterone gel) for the treatment of men with low testosterone levels. Participants will apply the cream or gel to their torso for 30 days during each treatment period and at the start and finish of each of the treatment periods, participants will provide blood samples at pre-determined time points for the measurement of blood testosterone levels. This study aims to establish that AndroForte (R) 5 is equally effective as Testogel (R) 1% (considered to be the standard comparator for transdermal testosterone worldwide), in increasing the testosterone levels in men with low testosterone to within the normal circulating range.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 31525 0
Address 31525 0
Country 31525 0
Phone 31525 0
Fax 31525 0
Email 31525 0
Contact person for public queries
Name 14772 0
Michael Buckley
Address 14772 0
Lawley Pharmaceuticals
Unit 2, 15a Harrogate Street
West Leederville, WA 6007
Country 14772 0
Australia
Phone 14772 0
+61 (0)8 9388 0096
Fax 14772 0
+61 (0)8 9388 0098
Email 14772 0
michaelb@lawleypharm.com.au
Contact person for scientific queries
Name 5700 0
Gary Mulholland
Address 5700 0
C/O Lawley Pharmaceuticals,
Unit 2, 15a Harrogate Street
West Leederville
Western Australia
6007
Country 5700 0
Australia
Phone 5700 0
+61 (0)421 491 727
Fax 5700 0
+61 (0)8 9304 2565
Email 5700 0
gmctcwa@tpg.com.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