| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Hypoactive sexual desire disorder (HSDD) secondary to combined oral contraception use. |
|
| E.1.1.1 | Medical condition in easily understood language |
| Decreased sexual desire due to combined oral contraception use |
|
| E.1.1.2 | Therapeutic area | Diseases [C] - Female diseases of the urinary and reproductive systems and pregancy complications [C13] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 20.0 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10020933 |
| E.1.2 | Term | Hypoactive sexual desire disorder |
| E.1.2 | System Organ Class | 100000004873 |
|
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
| To evaluate the efficacy of DHEA (50 mg daily dose) relative to placebo in women with COC-associated distressing loss of sexual desire (HSDD secondary to COC use) as measured by Profile of Female Sexual Function (PFSF) Desire Domain. |
|
| E.2.2 | Secondary objectives of the trial |
• To evaluate self reported perception of low desire (Female Sexual Distress Scale-Revised [FSDS-R] item 13)
• To evaluate subjects treatment benefit
• To validate in a nested study PFSF: total scores and single items of PFSF for example:
- Factor analysis
- Construct validity (to include convergent validity and known-groups validity)
- Reliability of the PFSF domains
- Responsiveness of the PFSF domains
- Responder definition for the PFSF Desire Domain through an anchor-based approach using Patient Global Impression of Change (PGIC) question and Subject's Meaningful Benefit Question as anchors
- Verification/test whether previously published threshold of 5 or less indicates low desire on the PFSF Desire Domain by use of receiver operating characteristic (ROC) curve analysis.
• To evaluate effect of DHEA-S treatment on endocrine parameters as a variable of restored sexual desire
|
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
Treatment Period 1
1. Women aged 18 to 45 who want to start a COC for contraception and who are willing to use a COC for 6 subsequent cycles.
2. Women reporting a satisfying sexual life and who are in a
monogamous, sexually active relationship for at least 6 months.
3. Women with normal sexual function at screening and at enrollment
visit, defined as
a. FSFI-6 >19 and
b. FSFI-6 Desire item ≥ 3 [i.e., score on 6-item Female Sexual Function
Index (FSFI-6) >19 with Desire (1st Item, level of sexual interest) = 3
or higher (1 or 2 = very low or none at all, or low; maximum score = 5)]
4. Good physical and mental health as judged by the investigator
through prospective evaluation at screening (medical history, physical
and gynecological (including breast) examination, clinical laboratory and
vital signs).
5. Premenopausal women having regular menstrual cycles (21 to 35
days)
6. Monogamous partner who is without sexual dysfunction (per female
subject's report) and who is available to the subject at least half the
time every month.
7. Willing to give written informed consent
8. Women having a functional relationship as per investigator judgement
(considering all information, e.g. interview with the clinician, LockeWallace Marital Adjustment Test [MAT] and Decreased Sexual Desire Screener [DSDS]).
9. Negative serum pregnancy test at screening and negative urine pregnancy test at enrollment visit.
10. Agree to not donate any blood or blood products during the study and in the 3 months after this study.
Treatment Period 2
1. Decreased sexual function (desire) due to COC use defined as:
a) Merits diagnosis of COC-associated HSDD on Decreased Sexual Desire
Screener (DSDS-OC) and
b) FSFI-6 Desire item < 3
2. Good physical and mental health as judged by the investigator
through prospective evaluation (physical and gynecological (including
breast) examination, clinical laboratory and vital signs)
3. Same monogamous partner as during treatment period 1 who is
without sexual dysfunction (per female subject's report) and who is
available to the subject at least half the time every month
4. Women continue to have a functional relationship as per subject
report
5. Negative urine pregnancy test at 2nd baseline (Visit 8). |
|
| E.4 | Principal exclusion criteria |
Treatment Period 1
1. Use of any hormonal contraceptive method in the prior 3 mths
2. Use of depot or injectable hormonal contraception in the prior 6 mths
3. History of or diagnosed with psychosis, depression or anxiety as per
medical history and interview with the clinician
4. Regular use within 6 mths before screening, or current use, of any
medication regularly associated with sexual dysfunction or known to
affect sexual arousal or desire (per protocol)
5. Chronic or acute life stress including planned surgery or other medical
procedures that interferes with sexual function or sexual activity
6. Androgen therapy, using OTC anabolic steroids within 3 mths prior to
screening, topical testosterone within 7 days before screening
7. Moderate, severe or cystic acne; clinically significant hirsutism; male pattern hair loss
8. Hyperandrogenic conditions (per protocol)
9. Lactation, pregnancy; or status post-partum or post-abortion within 6
mths before screening; intention to become pregnant during the study
10. Abnormal cervical smear (except: ASCUS with negative reflex HPV
test)
11. Clinically significant abnormal laboratory results at screening in the
opinion of the investigator, including fasting serum glucose
12. History of, or diagnosed with alcohol or drug abuse within 12 mths
before screening
13. Any arterial hypertension defined by blood pressure values of a)
systolic blood pressure ≥ 140 mmHg and /or b) diastolic blood pressure
≥ 90 mmHg
14. Diabetes mellitus, systemic lupus erythematosus; chronic
inflammatory bowel disease, dyslipoproteinemia requiring active
treatment with antilipidemic agent, hemolytic uremic syndrome, sickle
cell disease, Sydenham's chorea
15. Contraindication and risks for contraceptive steroids (per protocol)
16. Treatment with anticoagulants during the study and within 2 weeks
before screening
17. Use of any drug within 2 weeks before screening potentially
triggering interactions with COC
18. Any disease or condition that could result in altered absorption,
excessive accumulation, impaired metabolism, or altered excretion of
the investigational products (IPs)
19. Has any urologic or gynecologic condition that may, in the
investigator's opinion, affect sexual activity and/or function
20. Uncontrolled thyroid disorders or abnormal clinically significant TSH
at screening
21. AST and/or ALT results ≥1.5 x ULN or total serum bilirubin >1.5 x
ULN at screening
22. ≥ 3 recurrent vaginal or urinary infection within 1 year prior to
screening
23. Malignant disease except well treated squamous or basal cell cancer
of the skin
24. Severe renal condition or eGFR <60 mL/min at screening
25. Galactose, fructose, lactose intolerance
26. Subjects who have used any investigational drug in any clinical trial
within 3 mths prior to the first dose of COC or within five-times the halflife period of the drug used in previous study, whichever is
longer
27. Positive UDS at screening
Treatment Period 2
1. Development of another female sexual dysfunction that predominates
clinically over HSDD secondary to hormonal contraceptive use
2. Use of any other hormonal contraceptive method or hormonal
medications other than the dispensed LNG/EE study drug in the
treatment period 1
3. Development of psychosis, depression or anxiety; or another
psychiatric disorder or new life stress that interferes with sexual
function/ activity during treatment period 1
4. Initiation of any medication during treatment period 1 that interferes
with sexual function
5. Moderate, severe or cystic acne; clinically significant hirsutism; male
pattern hair loss
6. Hyperandrogenic conditions (per protocol)
7. Pregnancy
8. Clinically significant abnormal laboratory results prior to 2nd baseline
(at Visit7) in the opinion of the investigator
9. Arterial hypertension (per protocol)
10. Development of diabetes mellitus, systemic lupus erythematosus;chronic inflammatory bowel disease, dyslipoproteinemia requiring active treatment with antilipidemic agent, hemolytic uremic syndrome, sickle cell disease,Sydenham's chorea
11. Development of medical condition that may contribute to impaired sexual activity and function and, in the investigator's opinion, be the primary cause of sexual dysfunction
12. Development of medical condition that would cause risk or
contraindication to COC (per protocol)
13. Development of any disease or condition that could result in altered absorption, excessive accumulation,impaired metabolism, or altered excretion of the IPs
14. Use of any prohibited medication during treatment period 1
15. AST and/or ALT results ≥1.5 x the ULN or total serum bilirubin >1.5 x ULN prior to 2nd baseline at Visit 7
16. Development of malignant disease except well treated squamous or
basal cell cancer of the skin
17. Development of severe renal condition or eGFR<60 mL/min prior to
2nd baseline (Visit7)
18. Development of galactose,fructose,lactose intolerance |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| PFSF Desire Domain, change from baseline |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
| Change from treatment period 2 baseline to Day 168 |
|
| E.5.2 | Secondary end point(s) |
• FSDS-R item 13, change from baseline
• Proportion of subjects answering the Patient’s Meaningful Benefit Question as “yes”
• PFSF Responsiveness domain, change from baseline
• PFSF Arousal domain, change from baseline
• PFSF Orgasm domain, change from baseline
• PFSF Pleasure domain, change from baseline
• PFSF Concerns domain, change from baseline
• PFSF Self-image domain, change from baseline
• PFSF total score, change from baseline
• Endocrine parameters: absolute levels and change from screening to final cycle in treatment period 1 and change from final cycle in treatment period 1 to final cycle in treatment period 2, correlation with efficacy parameters
|
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
Change from treatment period 2 baseline to Day 168
Endocrine timepoints: Change from screening to final cycle in treatment period 1 and change from final cycle in treatment period 1 to final cycle in treatment period 2 |
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | No |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | No |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | No |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | Yes |
| E.7.3 | Therapeutic confirmatory (Phase III) | No |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | No |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | Yes |
| E.8.1.5 | Parallel group | Yes |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | No |
| E.8.2.2 | Placebo | Yes |
| E.8.2.3 | Other | No |
| E.8.2.4 | Number of treatment arms in the trial | 2 |
| E.8.3 |
The trial involves single site in the Member State concerned
| No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 12 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 55 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | No |
| E.8.6.2 | Trial being conducted completely outside of the EEA | No |
| E.8.7 | Trial has a data monitoring committee | No |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 2 |
| E.8.9.1 | In the Member State concerned months | 9 |
| E.8.9.1 | In the Member State concerned days | 12 |
| E.8.9.2 | In all countries concerned by the trial years | 2 |
| E.8.9.2 | In all countries concerned by the trial months | 9 |
| E.8.9.2 | In all countries concerned by the trial days | 12 |
Print
