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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Trimel Biopharma SRL
ClinicalTrials.gov Identifier:
NCT01364623
First received: May 27, 2011
Last updated: June 4, 2012
Last verified: June 2012
  Purpose

The purpose of this study is 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 will also be conducted.


Condition Intervention Phase
Female Sexual Dysfunction
Drug: Low dose testosterone nasal gel
Drug: Medium dose testosterone nasal gel
Drug: High dose testosterone nasal gel
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: An Open-label, Single and Multiple Application of Intranasal Testosterone Gel (TBS-2) in Healthy Premenopausal Female Subjects at Three Dose Levels

Resource links provided by NLM:


Further study details as provided by Trimel Biopharma SRL:

Primary Outcome Measures:
  • Area under the plasma concentration curve (AUC) of testosterone following TBS-2 [ Time Frame: up to 3 days ] [ Designated as safety issue: No ]
    The following pharmacokinetic parameters will be calculated: Cmax, Tmax, AUC, half life


Secondary Outcome Measures:
  • Area under the plasma concentration versus time curve (AUC) of dihydrotestosterone and estradiol following TBS-2 [ Time Frame: up to 3 days ] [ Designated as safety issue: No ]
    The following pharmacokinetic parameters will be calculated: AUC, Cmax, Tmax, half life

  • Number of subjects with adverse events [ Time Frame: Up to 5 days ] [ Designated as safety issue: Yes ]
    1. Vital Signs and Adverse Events: Blood Pressure, Body Temperature, Respiratory Rate, Heart Rate.
    2. Otorhinolaryngological examination with the nasal tolerance data presented in summary tables.
    3. Complete Blood Count: white blood count, hemoglobin and hematocrit.
    4. Clinical chemistry profile: Sodium, potassium, chloride, glucose, urea, creatinine, calcium, phosphate, uric acid, total bilirubin, albumin, AST, ALT, ALP, GGT, CK and cholesterol, hormone profiles.
    5. Urinalysis


Enrollment: 24
Study Start Date: September 2011
Study Completion Date: February 2012
Primary Completion Date: January 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Low dose TBS-2 Drug: Low dose testosterone nasal gel
Single dose administration
Other Name: TBS-2
Experimental: Medium dose TBS-2 Drug: Medium dose testosterone nasal gel
Single dose Administration
Other Name: TBS-2
Drug: Medium dose testosterone nasal gel
multiple dose administration
Other Name: TBS-2
Experimental: High dose TBS-2 Drug: High dose testosterone nasal gel
single dose Administration
Other Name: TBS-2

Detailed Description:

This is a 2 Period study that requires overnight stays in clinic. Blood samples are required at all visits including sampling at predefined time periods during the overnight stays.

Period I

Subjects will be checked-in on Day 1 Period I to start their baseline testosterone measurement (dependant on menstrual cycle, preferably within 48hr of start of the menstrual cycle). They will remain institutionalized until Day 4 morning, and will be checked out after the 48 hour blood draw and study close-out for those that do not continue with Period II.

Period II (Multi-Dose)

Subjects will be institutionalized starting on Day 1 of Visit 3 until Day 5 morning of Visit 3, and will be checked out after the 48 hour blood draw and study close-out.

  Eligibility

Ages Eligible for Study:   18 Years to 40 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria

  • 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

Exclusion Criteria

  • 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.
  • Any history of drug abuse or alcohol abuse as per DSM-IV criteria within 6 months of study drug administration.
  • Current treatment with any hormone replacement therapy within previous 12 months, treatment with drugs which interfere with metabolism of Testosterone within 30 days of study drug administration and/or any other prescription medications. Difficulty in abstaining from OTC medication for the duration of study.
  • Use of oral, transdermal and implant contraceptives within 30 days prior to drug administration or a depot contraceptives injection within one year prior to drug administration.
  • Evidence of pregnancy or lactation.
  • Subjects who are breast feeding or have breast fed within the last six (6) months prior to the Screening Visit.
  • Administration of another investigational drug within 30 days prior to study medication administration.
  • Blood donation within 56 days prior to study medication administration.
  • Any participation as a plasma donor in a plasmapheresis program within seven days preceding screening in this study.
  • Intolerance to venipuncture.
  • History of abnormal bleeding tendencies or thrombophlebitis unrelated to venipuncture or intravenous cannulation.
  • History of Deep Venous Thrombosis or coagulation disorders.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01364623

Locations
United States, Texas
Premier Research International LLC
Austin, Texas, United States, 78705
Sponsors and Collaborators
Trimel Biopharma SRL
Investigators
Study Director: Natalia Tkachenko, MD Trimel Pharmaceuticals Corporation
  More Information

No publications provided

Responsible Party: Trimel Biopharma SRL
ClinicalTrials.gov Identifier: NCT01364623     History of Changes
Other Study ID Numbers: TBS-2-2011-01
Study First Received: May 27, 2011
Last Updated: June 4, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by Trimel Biopharma SRL:
testosterone
pharmacokinetics

Additional relevant MeSH terms:
Testosterone
Testosterone enanthate
Testosterone undecanoate
Testosterone 17 beta-cypionate
Methyltestosterone
Androgens
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Pharmacologic Actions
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Therapeutic Uses
Anabolic Agents

ClinicalTrials.gov processed this record on August 27, 2014