Plain English Summary
Background and study aims
Hypoactive Sexual Desire Disorder is a problem affecting many women. These women have extremely low or no sexual desire and they are very distressed by this. If your low sexual desire is caused by a bad relationship with your partner, a high amount of stress, another illness that you have, or it is a side effect of medication that you are taking, you do not have Hypoactive Sexual Desire Disorder. There are several medications being tested to see if they help solve these problems in sexual desire. One of these medications has two active ingredients: testosterone and sildenafil. Testosterone and sildenafil have to be taken in two different ways because otherwise, the medication doesn’t work. The testosterone is dissolved under the tongue and the sildenafil tablet is swallowed. In earlier studies, these two ingredients were administered separately (the old way). Now a tablet has been made that combines these two ingredients into one tablet (the new way). This study investigates if these two different ways of taking the medication, the old way and the new way, are the same. This is done by comparing the blood levels of testosterone and sildenafil in women who take the medication in the old way and in the new way.
Who can participate?
Healthy women between the ages of 18 and 35.
What does the study involve?
The women are first screened by a physician to see if they are eligible to participate in the study. If so, they are invited to the research centre for two overnight visits. During the first overnight visit they are given the medication in the old or new form. Just before taking the medication blood is drawn. After taking the medication, blood is drawn another 27 times over a period of 26 and a half hours. During the second overnight visit, the women are given the other medication form and blood is drawn in the same way as the first visit. The subjects blood is sent to a laboratory where it is tested for how much of each drug is in the blood at different points in time.
What are the possible benefits and risks of participating?
The participants are given 828 Euros for participation and a fixed fee of 38 Euros for travel expenses. A total amount of 246.2 ml of blood is drawn from each participant during the entire study. Participants may experience side effects from the medication. The most common side effects are headache, flushing, nausea, a runny nose and dizziness.
Where is the study run from?
University Medical Center Groningen ( Netherlands).
When is the study starting and how long is it expected to run for?
December 2010 to July 2011.
Who is funding the study?
Emotional Brain B.V. (Netherlands).
Study website
Contact information
Type
Scientific
Contact name
Dr Jos Bloemers
ORCID ID
http://orcid.org/0000-0001-5637-7606
Contact details
Emotional Brain BV
Louis Armstrongweg 78
Almere
1311 RL
Netherlands
+31 (0)36 - 546 83 46
j.bloemers@emotionalbrain.nl
Additional identifiers
EudraCT/CTIS number
2011-000457-23
IRAS number
ClinicalTrials.gov number
Nil known
Protocol/serial number
EB81, NL35616.044.11
Study information
Scientific title
A randomized, cross-over controlled study to compare the pharmacokinetic profiles of sublingual administered testosterone solution followed by a sildenafil citrate tablet, versus sublingual testosterone and sildenafil citrate combined in one tablet in healthy premenopausal women
Acronym
Study hypothesis
1. Primary objective: To compare the pharmacokinetics of testosterone and sildenafil citrate given as a sublingual solution of testosterone with an encapsulated tablet of sildenafil (formulation 1 = F1) versus a combination product, containing both testosterone and sildenafil in one tablet (formulation 2 = F2).
2. Secondary objective: To investigate the time frame in which the mint flavored testosterone coating is dissolved.
Ethics approval(s)
Medisch Ethische Toetsingscommissie Twente (Enschede, The Netherlands). Medical Ethics Review Board Twente, 20/05/2011, ref: METC/11179.kop
Study design
Single-center, randomized, cross-over controlled study.
Primary study design
Interventional
Secondary study design
Randomised cross over trial
Study setting(s)
Other
Study type
Other
Patient information sheet
Not available in web format, please use the contact details to request a participant information sheet
Condition
Hypoactive sexual desire disorder
Intervention
1. Testosterone (0.5mg) and sildenafil (50mg) administered separately as a solution containing testosterone for sublingual administration followed 2 1/2 hours later by a tablet containing sildenafil for oral administration
2. Testosterone (0.5mg) and sildenafil (50mg) administered in a single fixed-dose combination tablet
Intervention type
Drug
Pharmaceutical study type(s)
Phase
Phase I
Drug/device/biological/vaccine name(s)
Lybrido
Primary outcome measure
Pharmacokinetic (PK) parameters for total testosterone, free testosterone and dihydrotestosterone as well as for sildenafil and Ndesmethyl-sildenafil:
1. Maximum concentration (Cmax)
2. Area under the plasma concentration curve (AUC0-infinity/ AUC0-1590)
3. Time to Cmax (Tmax)
The total testosterone and dihydrotestosterone were analyzed in plasma in a combination assay using High Performance Liquid Chromatography Tandem Mass Spectrometry (HPLCMS/MS). Free testosterone was determined in plasma through ultra filtration followed by LCMS/MS. Incurred sample reanalysis was performed in 5% of all samples. The existing method of analysis has been validated in a prior study.
The analytes Sildenafil and N-desmethyl-sildenafil in human plasma were determined by means of a HPLC-MS/MS. Incurred sample reanalysis was performed in 10% of all samples.
Samples were analysed using a mobile phase containing water, methanol and 0.1% acetic acid. The analytical column Hypersil GOLD (Thermo Scientific), dimension 50 x 2.1 mm, particle size 3 µm was used. An API-4000 triple quadrupole tandem mass spectrometer (Applied Biosystems) was used as the detector.
Secondary outcome measures
Safety assessments including:
1. Standard clinical chemistry, hematology and serology tests
2. Vital signs
3. Electrocardiogram (ECG)
4. Body temperature
5. Physical examination
Overall study start date
01/12/2010
Overall study end date
15/07/2011
Reason abandoned (if study stopped)
Eligibility
Participant inclusion criteria
Subject had to fulfill all of the following criteria to be enrolled into the study:
1. Provide written informed consent
2. Be female, between 18 and 35 years of age inclusive
3. Be healthy based on medical history, physical examination, laboratory values and vital signs
4. Have a body mass index (BMI) 18 kg/m2 and 30 kg/m2
5. Have sufficient venous access to allow blood draws
Participant type(s)
Healthy volunteer
Age group
Adult
Lower age limit
18 Years
Upper age limit
35 Years
Sex
Female
Target number of participants
12
Total final enrolment
12
Participant exclusion criteria
Subjects could not be entered into the study if any of the following criteria were met:
1. Cardiovascular conditions:
1.1. Any underlying cardiovascular condition, including unstable angina pectoris
1.2. History of myocardial infarction, stroke, or life-threatening arrhythmia within 6 months prior to study entry
1.3. Uncontrolled atrial fibrillation/flutter at screening or other significant abnormality observed on electrocardiogram (ECG)
1.4. Systolic blood pressure 140 mmHg and/or diastolic blood pressure > 90 mmHg
1.5. Systolic blood pressure < 90 mmHg and/or diastolic blood pressure <50 mmHg
2. Gynecological and obstetric conditions:
2.1. Use of oral contraceptive containing anti-androgens
2.2. Use of oral contraceptive containing 50 g estrogen or more
2.3. Pregnancy or intention to become pregnant during this study (Note: All women were to undergo a urine pregnancy test prior to study entry)
2.4. Lactating or delivery in the previous 6 months
2.5. Unexplained gynecological complaints, such as clinically relevant abnormal uterine bleeding patterns
2.6. Subjects with a perimenopausal hormonal status (follicle-stimulating hormone > 30)
3. Other medical conditions:
3.1. Liver and/or renal insufficiency
3.2. Current clinically relevant endocrine disease
3.3 Current clinically relevant neurological disease which, in the opinion of the investigator, would compromise the validity of study results, or which could constitute a contraindication for sildenafil and/or testosterone use
3.4. History of hormone-dependent malignancy
4. Psychological/psychiatric factors:
4.1. A substance abuse disorder that, in the opinion of the investigator, was likely to affect the subject’s ability to complete the study or preclude the subject’s participation in the study; mild or moderate alcohol consumption was allowed but had to be stopped 24 hours before the admission period until follow up. Smokers were not allowed to participate.
5. Concomitant medication:
5.1. Subjects who were taking CYP3A4-inhibitors (e.g., ritonavir, ketoconazole, itraconazol claritromycine, erytromycine and saquinavir)
5.2. Subjects who were taking CYP3A4-inducers (e.g., carbamazepine, fenytoinefenobarbital, St Johns Wort, rifampicine)
5.3. Use of nitrates or nitric oxide donor compounds
5.4. Use of any other medication that could interfere with study medication (e.g., monoamine oxidase (MAO) inhibitors (includes classic MAO inhibitors and linezolid), calcium channel blockers (e.g., diltiazem and verapamil), use of corticosteroids)
5.5. Use of testosterone therapy within 6 months before study entry
6. Drug/food interaction
6.1. Consumption of grapefruit or grapefruit-containing foods throughout the duration of the study
7. General:
7.1. Illiteracy, unwillingness, or inability to follow study procedures
7.2. Any other clinically significant abnormality or condition which, in the opinion of the investigator, might interfere with the subject’s ability to provide informed consent or comply with study instructions, compromise the validity of study results, or be a contraindication of sildenafil and/or testosterone use
7.3. Participation in any other clinical drug study in the previous 3 months
Recruitment start date
16/06/2011
Recruitment end date
24/06/2011
Locations
Countries of recruitment
Netherlands
Study participating centre
QPS Groningen
University Medical Center Groningen, Biotech Center
Hanzeplein 1 - input 53
Groningen
9713 GZ
Netherlands
Sponsor information
Organisation
Emotional Brain BV
Sponsor details
Louis Armstrongweg 78
Almere
1311RL
Netherlands
Sponsor type
Research organisation
Website
ROR
Funders
Funder type
Research organisation
Funder name
Emotional Brain BV (The Netherlands)
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Results and Publications
Publication and dissemination plan
We plan to publish these results in 2015. We have submitted to PLOS ONE and are awaiting a trial ID before it can move ahead to the next stage of review.
Intention to publish date
Individual participant data (IPD) sharing plan
IPD sharing plan summary
Not provided at time of registration
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Results article | 07/03/2016 | 17/05/2023 | Yes | No |