A Open-Label, Within-Subject Dose-Escalation Study to Evaluate the Clinical Safety and Pharmacokinetic Profile of a Topical Sildenafil Cream (5% w/w), in Healthy Postmenopausal Women

NCT02364882 | Completed Phase 1

• 1 other identifier: SST-6006-008-01
• Study Type: interventional
• Target: 21
• Locations: 1 country
• Sites: 1

Brief Summary

This is a Phase 1, single center, open-label, within-subject dose-escalation study evaluating the safety and pharmacokinetics of SST-6006 in healthy postmenopausal women. Three dose levels of SST-6006 and a placebo regimen will be evaluated: 1 g (0 mg of sildenafil), 1 g (50 mg of sildenafil), 2 g (100 mg of sildenafil), and 4 g (200 mg of sildenafil). Doses will be administered sequentially and will be separated by a 14-16 day washout period. All 3 dose levels and the placebo will be applied both externally and internally.

Conditions

Female Sexual Health

Outcome Measures

Primary Outcomes (3)

• Vaginal Irritation

  • Occurrence of vulvar-vaginal reactions documented on the vaginal safety questionnaire By Berger Bowman rating and AEs

  32 hours

• Orthostatic Hypotension

  Vital sign measurement

  32 Hours

• Incidence of AEs

  Adverse events, including occurrence of headache, orthostatic hypotension, flushing, dyspepsia, nasal congestion, urinary tract infection, abnormal vision (chromatopsia,increased sensitivity to light, blurred vision), diarrhea, dizziness, and rash

  32 hours

Secondary Outcomes (3)

• Cmax,

  32 hours

• AUC

  32 hours

• T 1/2

  32 hours

Study Arms (4)

1

PLACEBO COMPARATOR

1 g (placebo) 0 mg sildenafil 50% external (i.e. labia minora and clitoral area) / 50% intravaginal

Drug: Sildenafil

2

ACTIVE COMPARATOR

1 g 50 mg sildenafi 50% external (i.e. labia minora and clitoral area) / 50% intravaginal

Drug: Sildenafil

3

ACTIVE COMPARATOR

2 g 100 mg sildenafi 50% external (i.e. labia minora and clitoral area) / 50% intravaginal

Drug: Sildenafil

4

ACTIVE COMPARATOR

4 g 200 mg sildenafi 50% external (i.e. labia minora and clitoral area) / 50% intravaginal

Drug: Sildenafil

Interventions

Sildenafil DRUG

1; 2; 3; 4

Eligibility Criteria

• Age: 35 Years - 65 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subject must be postmenopausal (surgically induced or natural) between the ages of 35 and 65 years, inclusive, verified by 1 of the following:
• Surgical oophorectomy, partial hysterectomy, or full hysterectomy at least 1 year prior to screening (self-report).
• No spontaneous menses \> 1 year (self-report).
• Subject must have a serum follicle-stimulating hormone (FSH) lab result \> 40mIU/mL.
• Subject has a body mass index (BMI) from 18 to 33 kg/m², inclusive.
• Subject has a normal electrocardiogram at baseline.
• Subject has had a Pap smear performed within one year prior to the Screening visit and can provide documentation indicating normal test results.
• If the subject cannot provide documentation, a Pap smear will be performed at Screening. Subjects with abnormal findings will be excluded from study participation and be referred for follow-up medical care as appropriate.
• Subject is in good health for age, as determined by medical and Ob-Gyn history and physical and gynecological examinations.
• As part of the gynecological exam the subject must have a pain intensity score of 0 with the cotton swab test in the lower vagina, labia majora, and labia minora when asked about pain intensity on the 0 -¬ 10 verbal rating scale when gently pressing cotton swab. Also with the cotton swab test to assess tenderness within the vulvar vestibule the score must be similarly 0 on the pain intensity score on the 0 ¬ 10 verbal rating scale when gently pressing the cotton swab at 2, 5, 7 and 10 o'clock position within the vulvar vestibule.
• Subject is a non-smoker (no tobacco use within 6 months) and agrees not to smoke for the duration of the study up until completion of the last Treatment Period.
• Subject is capable of understanding and complying with the protocol and agrees to sign the informed consent document.
• Subject agrees to abstain from sexual activity (anal, oral, or vaginal) for one week after discharge for each Treatment Period to avoid potential partner exposure to the investigational product.
• Subjects must agree to not use vaginal or vulvar lubricants, spermicides, creams or gels, foams or vaginal douche products for the duration of the study.

You may not qualify if:

• Subject has any disorder or a history of any disorder that may prevent the successful completion of the study in the opinion of the PI.
• Subject has a significant cardiovascular, hepatic, renal, respiratory, gastrointestinal, endocrine, immunologic, dermatologic, hematologic, neurologic, genitourinary, or psychiatric disease or other unstable medical condition that would contraindicate administration of study medication, interfere with study evaluation, limit study participation, or confound the interpretation of study results in the opinion of the PI.
• Subject has a history of sexual or physical abuse.
• Subject had an active ulcer or clinically significant bleeding disorder.
• Subject has a history of myocardial infarction, stroke, or life-threatening arrhythmia within 6 months prior to Day 1; or any history of coronary disease causing angina; or congestive heart failure requiring medical intervention.
• Subject has retinitis pigmentosa or sickle cell anemia or related anemias, even if the subject feels clinically well at the time of Screening. Subjects with retinitis pigmentosa will be identified by specifically asking whether they have the condition, if there are visual signs and symptoms of the condition (including questioning subjects as to whether they have difficulty seeing at night or in low light, and if they have any visual field deficits that indicate a loss of peripheral or central vision), or if there is a family history.
• Subject has a history of orthostatic hypotension or orthostatic hypotension which is present at the Screening visit, defined as a drop in systolic blood pressure ≥ 20 mm Hg, a drop in diastolic blood pressure ≥ 10 mm Hg or experiencing lightheadedness or dizziness at 1 or 3 minutes after the change in position from supine to standing.
• Subject has untreated hypertension.
• Subject has type 1 or type 2 diabetes.
• Subject has a history of cancer, other than basal cell carcinoma.
• Subject has any surgical or medical condition that may interfere with the absorption, distribution, metabolism, or excretion of the test article in the opinion of the PI.
• Subject has a history of drug abuse within 1 year before Day 1.
• Subject has a history of alcoholism within 1 year before Day 1, admitted alcohol abuse, average consumption of more than 1 standard unit of alcohol per day (a standard unit equals 12 ounces of beer, 1½ ounces of 80-proof alcohol, or 6 ounces of wine).
• Subjects who have a history of non-arteritic ischemic optic neuropathy (NAION)
• Subject has had treatment currently or within 1 month (28 days) prior to Day 1 with any of the following: weak, moderate, and strong inhibitors and inducers of CYP3A4 and CYP2C9 enzymes (e.g., CYP3A4: ketoconazole, clarithromycin, verapamil, diltiazem, St. John's Wort / CYP2C9: fluconazole, oxandrolone, fluvastatin, and metronidazole). Any prescription, over-the-counter (OTC) medications, or herbal products taken recently or currently being taken will be screened by study personnel prior to study enrollment to confirm such drugs do not inhibit or induce the 2 enzymes listed above. If the subject takes any prescription or OTC drugs at the direction of a health care provider that are inhibitors or inducers of CYP3A4 and CYP2C9, that provider should be consulted before medications are stopped for the purposes of study participation.

Sponsors & Collaborators

• Strategic Science & Technologies, LLC: lead

Study Sites (1)

Clinical Pharmacology of Miami, Inc.

Miami, Florida, 33014-3616, United States

Location

MeSH Terms

Interventions

Sildenafil Citrate

Intervention Hierarchy (Ancestors)

Sulfonamides; Amides; Organic Chemicals; Sulfones; Sulfur Compounds; Piperazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Ken Lassseter, MD

  CPMI

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 27, 2015
• First Posted: February 18, 2015
• Study Start: January 1, 2015
• Primary Completion: May 1, 2015
• Study Completion: May 1, 2015
• Last Updated: June 22, 2015

Record last verified: 2015-06

Locations

US (1)