PK Study of Testosterone Nasal Gel (TBS-2) in Healthy Premenopausal Women

NCT01364623 | Completed Phase 1 Results DMC

• 1 other identifier: TBS-2-2011-01
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study was to assess the bioavailability of total testosterone through pharmacokinetic profiles obtained following (a) single administration of three doses of TBS-2 b) multiple administration TBS-2. In addition, assessing the bioavailability of free testosterone, dihydrotestosterone, SHBG and estradiol through pharmacokinetic profiles was also conducted.

Conditions

Female Sexual Dysfunction

Keywords

testosterone; pharmacokinetics

Outcome Measures

Primary Outcomes (3)

• Bioavailability (AUC0-t) of Total Testosterone Through Pharmacokinetic (PK) Profiles

  Area under the concentration time curve from time zero to the last measurable concentration time point (AUC0-t) for single dose and AUCtau shown for multiple dose.

  Based on blood samples collected -0.25, 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 12, 16, 20, 23.5h relative to dosing

• Bioavailability (Cmax) of Total Testosterone Through Pharmacokinetic Profiles

  Cmax - maximum concentration of total testosterone observed after dosing of TBS-2

  Based on blood samples collected -0.25, 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 12, 16, 20, 23.5h relative to dosing

• Medium Dose TBS-2 Multiple Dose Average Steady-state Concentration (Cavg) of Total Testosterone

  -0.25, 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 12, 16, 20, 24, 32, 40, 48h after Day 3 dosing

Secondary Outcomes (2)

• Area Under the Plasma Concentration Versus Time Curve (AUC) for Dihydrotestosterone Following TBS-2

  Based on blood samples collected -0.25, 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 12, 16, 20, 23.5h relative to dosing

• Area Under the Plasma Concentration Versus Time Curve (AUC) for Estradiol Following TBS-2

  Based on blood samples collected -0.25, 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 12, 16, 20, 23.5h relative to dosing

Study Arms (4)

Low dose TBS-2 single dose

EXPERIMENTAL

TBS-2 dispensers prefilled with 0.24% testosterone gel to deliver a single dose of 300 μg of testosterone per nostril, for a total dose of 600 μg given at 0800 hours (±30 minutes) on Day 2 of Period 1 for Cohort 1 (Low dose testosterone nasal gel, single dose)

Drug: Low dose testosterone nasal gel, single dose

Medium dose TBS-2 single dose

EXPERIMENTAL

TBS-2 dispensers prefilled with 0.48% testosterone gel to deliver a single dose of 600 μg of testosterone per nostril, for a total dose of 1200 μg given at 0800 hours (±30 minutes) on Day 2 of Period 1 for Cohort 2 (Medium dose testosterone nasal gel, single dose)

Drug: Medium dose testosterone nasal gel, single dose

High dose TBS-2 single dose

EXPERIMENTAL

TBS-2 dispensers prefilled with 0.72% testosterone gel to deliver a single dose of 900 μg of testosterone per nostril, for a total dose of 1800 μg given at 0800 hours (±30 minutes) on Day 2 of Period 1 for Cohort 3 (High dose testosterone nasal gel, single dose)

Drug: High dose testosterone nasal gel, single dose

Medium dose TBS-2 multiple doses

EXPERIMENTAL

TBS-2 dispensers prefilled with 0.48% testosterone gel to deliver a single dose of 600 μg of testosterone per nostril, for a total dose of 1200 μg given t.i.d. daily at 0800 hours (± 30 minutes), 1600 hours (± 30 minutes), and 2400 hours (± 30 minutes) on Days 1 and 2 of Period 2, and once in the morning at 0800 hours (± 30 minutes) on Day 3 of Period 2 (Multi-dose group) (Medium dose testosterone nasal gel, multiple dose)

Drug: Medium dose testosterone nasal gel, multiple dose

Interventions

Low dose testosterone nasal gel, single dose DRUG

Low dose testosterone nasal gel, single dose

Also known as: TBS-2

Low dose TBS-2 single dose

Medium dose testosterone nasal gel, single dose DRUG

Medium dose testosterone nasal gel, single dose

Also known as: TBS-2

Medium dose TBS-2 single dose

High dose testosterone nasal gel, single dose DRUG

High dose testosterone nasal gel, single dose

Also known as: TBS-2

High dose TBS-2 single dose

Medium dose testosterone nasal gel, multiple dose DRUG

Medium dose testosterone nasal gel, multiple dose

Also known as: TBS-2

Medium dose TBS-2 multiple doses

Eligibility Criteria

• Age: 18 Years - 40 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Subjects having regular menstrual cycles between 26-32 days.
• Women of childbearing potential must agree to use one of the following reliable birth control methods prior to the study, during the study and up until one month after the end of the study:
• Surgically sterile
• Intrauterine device in place for at least 3 months prior to study initiation
• Barrier method (condom with spermicidal agent use by partner)
• Abstinence
• Negative for drugs of abuse, hepatitis B-surface antigen, hepatitis C, HIV, and pregnancy (serum ß-HCG).
• Body Mass Index greater than or equal to 18.5 kg/m² and less than or equal to 35 kg/m².
• Subjects with a normal ENT exam.
• Subjects with normal TSH values.
• No clinically significant findings in the physical examination, 12-lead ECG and vital signs
• Normal thyroid function. Physiological prolactin concentration.
• All clinical laboratory test values within the acceptable ranges (any clinically significant findings will require investigator/sponsor approval)
• Able to understand and provide written informed consent.
• Availability of the subject for the entire study period and willingness of the subject to adhere to protocol requirements, as evidenced by a signed ICF

You may not qualify if:

• Known history of hypersensitivity to Testosterone (e.g. Intrinsa patch) and/or related drugs.
• Known history of polycystic ovarian syndrome.
• Known history or presence of cardiac, pulmonary, gastrointestinal, endocrine, musculoskeletal, neurological, psychiatric, hematological, reproductive, liver or kidney disease, unless judged not clinically significant by the Principal Investigator or medical designate.
• Presence of or known history of Estrogen-responsive tumors such as breast cancer and /or history of any cancer, excluding basal cell carcinoma.
• Known history of frequent clinically significant acne.
• Known history of hirsutism
• History of nasal surgery, specifically turbinoplasty, septoplasty, rhinoplasty, "nose job", or sinus surgery.
• Prior nasal fractures.
• Active allergies, such as rhinitis, rhinorrhea, and nasal congestion.
• Mucosal inflammatory disorders, specifically pemphigus, and Sjogren's syndrome.
• Sinus disease, specifically acute sinusitis, chronic sinusitis, or allergic fungal sinusitis.
• History of nasal disorders or sleep apnea.
• Use of any form of intra-nasal medication delivery, specifically nasal corticosteroids and oxymetazoline containing nasal sprays
• History of Hepatitis B, a positive test for Hepatitis B surface antigen, a history of Hepatitis C, a positive test for Hepatitis C antibody, a history of HIV infection or demonstration of HIV antibodies.
• Any history of severe allergic reaction (including drugs, food, insect bites, environmental allergens or any condition known to interfere with the absorption, distribution, metabolism or excretion of drugs.

Sponsors & Collaborators

• Acerus Pharmaceuticals Corporation: lead

Study Sites (1)

Premier Research International LLC

Austin, Texas, 78705, United States

Location

Results Point of Contact

• Title: Dr. Nathan Bryson, Vice President, Scientific Affairs
• Organization: Acerus Pharmaceuticals Corporation

nbryson@aceruspharma.com

1-416-679-0776

Study Officials

• Natalia Tkachenko, MD

  Trimel Pharmaceuticals Corporation

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 27, 2011
• First Posted: June 2, 2011
• Study Start: September 1, 2011
• Primary Completion: January 1, 2012
• Study Completion: February 1, 2012
• Last Updated: October 16, 2019
• Results First Posted: September 13, 2019

Record last verified: 2019-10

Locations

US (1)