Plain English Summary
Background and study aims
Testosterone is the most powerful of the male sex hormones (androgens) and is responsible for the secondary sexual characteristics seen in men, such as a deeper voice and facial hair. Although testosterone is considered to be a “male hormone”, it is also produced in women, although in much smaller quantities. As men get older, testosterone levels fall. When a man has low testosterone, it can cause them to lose their sex drive, experience erectile dysfunction and even depression. In some cases a man may need to take artificial testosterone in order to maintain their natural levels (hormone replacement therapy). This type of therapy is usually given as an injection, as when pure testosterone is taken by mouth (orally) most of it is broken down and so doesn’t increase blood levels. A new form of oral testosterone has been developed into a tablet which is orodispersible (dissolves in the mouth). These tablets contain a chemical called hydroxypropyl-β-cyclodextrin (HPBCD) which helps them to dissolve in saliva so that the testosterone can be absorbed by the body. The aim of this study is to find out whether taking HPBCD orodispersible tablets (ODT) can help to increase levels of testosterone in the blood. The drug is being given to women who have been through the menopause (as they have much less testosterone than men with low testosterone levels).
Who can participate?
Healthy women between the ages of 45 and 65 who have been through the menopause.
What does the study involve?
Participants are randomly allocated into one of three groups, all of whom will receive each of the three treatments in a different order. The first treatment involves allowing a 6mg HPBCD ODT tablet to dissolve on the tongue, the second treatment involves allowing a 12mg HPBCD ODT tablet dissolve on the tongue and the third treatment involves swallowing a 12mg HPBCD ODT tablet with water. Participants wait for 3 days in between receiving each treatment (wash-out period). At regular intervals on the day that each dose is taken, participants have blood samples taken so that testosterone levels can be measured in the laboratory.
What are the possible benefits and risks of participating?
There are no benefits of participating in the study. There are no significant risks of participating, as the doses given are very small and unlikely to trigger unwanted side-effects.
Where is the study run from?
CROSS Research S.A. Phase I Unit (Switzerland)
When is the study starting and how long is it expected to run for?
July 2014 to October 2015
Who is funding the study?
IBSA Institut Biochimique S.A. (Switzerland)
Who is the main contact?
Dr Milko Radicioni
Trial website
Contact information
Type
Scientific
Primary contact
Dr Milko Radicioni
ORCID ID
http://orcid.org/0000-0002-3940-8375
Contact details
CROSS Research Phase I Unit
Via F. A. Giorgioli 14
Arzo
CH-6864
Switzerland
Additional identifiers
EudraCT number
ClinicalTrials.gov number
Protocol/serial number
CRO-PK-14-287
Study information
Scientific title
Bioavailability study of a new testosterone orodispersible tablet (ODT) administered as single doses of 6 and 12 mg to healthy postmenopausal women. Single dose, open, randomised, 3-period, 3-way cross-over exploratory bioavailability study
Acronym
Study hypothesis
The aim of this study is to evaluate the pharmacokinetic (PK) profile of the new oral testosterone ODT formulation administered under fasting conditions at the doses of 6 and 12 mg. The safety profile after single dose administration will be evaluated during the whole study.
Ethics approval
1. Ethics Committee Cantonale (Comitato Etico Cantonale), 15/09/2014, ref: CE2832
2. Federal Health Authorities (Swissmedic), 09/04/2015, ref: 2015DR1053
Study design
Single-dose open-randomised 3-period 3-way cross-over exploratory bioavailability study
Primary study design
Interventional
Secondary study design
Randomised cross over trial
Trial setting
Other
Trial type
Other
Patient information sheet
Condition
Healthy adult volunteers under fasting conditions
Intervention
The study was conducted in healthy post-menopausal women as a model to avoid the problem of endogenous levels and fluctuations of testosterone in the pharmacokinetics results. Post-menopausal women have in fact baseline testosterone levels of less than 1.00 ng/mL, as compared to hypogonadal men with levels of of less than 350 ng/dL.
Each volunteer received one single dose of the following test treatments in 3 periods separated by wash-out intervals of at least 3 days, for a minimum study duration of 9 days, screening visit included:
1. 1 testosterone HPBCD ODT 6 mg disintegrated on the tongue (without chewing)
2. 1 testosterone HPBCD ODT 12 mg disintegrated on the tongue (without chewing)
3. 1 testosterone HPBCD ODT 12 mg swallowed with water
The sequence of the 3 test treatments in the study periods was assigned to each volunteer according to a computer generated randomisation list. The follow-up was performed only in case of adverse events, until resolution or stabilization.
Intervention type
Drug
Phase
Phase I
Drug names
Testosterone hydroxypropyl-β-cyclodextrin (HPBCD)
Primary outcome measures
Baseline-corrected rate (Cmax) and extent (AUC0-t) of exposure of total testosterone, free-testosterone and 5α-dihydro-testosterone (DHT) after single dose administration of the test treatments at baseline, 10, 20, 30, 45 minutes, 1, 1.5, 2, 3, 4, 5, 6 and 8 hours post-dose
Secondary outcome measures
1. tmax and baseline-corrected AUC0-∞, t1/2, and λz of total testosterone, free-testosterone and DHT at baseline, 10, 20, 30, 45 minutes, 1, 1.5, 2, 3, 4, 5, 6 and 8 hours post-dose
2. Treatment-Emergent Adverse Events (TEAEs), vital signs (BP, HR), body weight, laboratory parameters (hormones included), ECG after administration of each test treatment.
Overall trial start date
08/07/2014
Overall trial end date
07/10/2015
Reason abandoned
Eligibility
Participant inclusion criteria
1. Women aged between 45 and 65 inclusive
2. Post-menopausal status for at least 1 year
3. Body Mass Index (BMI): 18.5-30 kg/m2 inclusive
4. Vital signs: systolic blood pressure 100-139 mmHg, diastolic blood pressure 50-89 mmHg, heart rate 50-90 bpm
5. Endogenous testosterone levels < 3.5 nmol/L (about 1.00 ng/mL)
6. Normal or not clinically relevant abnormal cervical smears at PAP test
7. Normal or not clinically relevant abnormal mammograms
8. Ability to provide informed consent
Participant type
Healthy volunteer
Age group
Adult
Gender
Female
Target number of participants
Sixteen (16)
Participant exclusion criteria
1. ECG 12-leads (supine position): clinically relevant abnormalities
2. Clinically relevant abnormal physical findings
3. Clinically relevant abnormal laboratory values
4. Ascertained or presumptive hypersensitivity to the active principle (testosterone) and/or formulations' ingredients
5. Relevant history of cardiovascular, pulmonary, hepatic, renal, haematological, gastrointestinal, immunological, dermatological, endocrine, genito-urinary, neurological or psychiatric diseases that could interfere with the aim of the study; malignant neoplasia
6. Intake of any drug affecting the cytochrome P450 for 28 days before the first dose
7. Any hormonal replacement therapy (estrogen-progestin formulations) within 4 weeks, any sex hormone depot injection within 6 months and any sex hormone implants within 5 years
Recruitment start date
27/04/2015
Recruitment end date
30/06/2015
Locations
Countries of recruitment
Switzerland
Trial participating centre
CROSS Research S.A
Phase I Unit
Via F.A. Giorgioli 14
Arzo
CH-6864
Switzerland
Funders
Funder type
Industry
Funder name
IBSA Institut Biochimique SA
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Results and Publications
Publication and dissemination plan
No intention to publish study results
Intention to publish date
Participant level data
Stored in repository
Results - basic reporting
Publication summary