Pharmacokinetic Evaluation of Brisdelle™ (Formerly Known as Mesafem) Following Single & Repeat Oral Administration in Healthy Postmenopausal Women (N30-005)

• ClinicalTrials.gov Identifier: NCT01829919
• Recruitment Status: Completed
• First Posted: April 11, 2013
• Results First Posted: February 24, 2014
• Last Update Posted: October 15, 2015
• Sponsor: Noven Therapeutics
• Information provided by (Responsible Party): Noven Therapeutics

Study Description

Brief Summary:

The purpose of this study is to assess the pharmacokinetics (absorption, breakdown and elimination from the body), safety and tolerability of Brisdelle (paroxetine mesylate) Capsules 7.5 mg when given as a single dose and multiple doses.

Condition or disease	Intervention/treatment	Phase
Postmenopausal Symptoms	Drug: Brisdelle (paroxetine mesylate)	Phase 1

Detailed Description:

This study is for research only and is not designed to treat a medical condition.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 24 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Evaluation of Pharmacokinetics of Paroxetine Following Single and Repeat Oral Administration of Mesafem (7.5 mg Paroxetine Mesylate) Capsules in Healthy Postmenopausal Women
• Study Start Date: July 2011
• Actual Primary Completion Date: August 2011
• Actual Study Completion Date: August 2011

Arms and Interventions

Arm	Intervention/treatment
Experimental: Brisdelle (paroxetine mesylate); Brisdelle (paroxetine mesylate) Capsules taken orally with 240 mL of water for 20 days.	Drug: Brisdelle (paroxetine mesylate); All subjects will receive Brisdelle (paroxetine mesylate) Capsules 7.5 mg, first as a single dose and then, following a five-day wash-out period, once per day for 14 days.; Other Names: Former Names: Mesafem capsules 7.5 mg or; LDMP (Low-Dose Mesylate salt of Paroxetine)

Outcome Measures

Primary Outcome Measures :

1. AUC (Hour*ng/mL) Single Dose Pharmacokinetics of Brisdelle™ (Paroxetine Mesylate) Capsules 7.5 mg [ Time Frame: Day 1 ]
2. Cmax (ng/mL) Single Dose Pharmacokinetics of Brisdelle™ (Paroxetine Mesylate) Capsules 7.5 mg [ Time Frame: Day 1 ]
3. Kel (Hour^-1) Single Dose Pharmacokinetics of Brisdelle™ (Paroxetine Mesylate) Capsules 7.5 mg [ Time Frame: Day 1 ]
4. Mean t1/2 Single Dose Pharmacokinetics of Brisdelle™ (Paroxetine Mesylate) Capsules 7.5 mg [ Time Frame: Day 1 ]
5. Median t1/2 Single Dose Pharmacokinetics of Brisdelle (Paroxetine Mesylate) Capsules 7.5 mg [ Time Frame: Day 1 ]
6. AUC (Hour*ng/mL) Multiple Dose Pharmacokinetics of Brisdelle (Paroxetine Mesylate) Capsules 7.5 mg [ Time Frame: Day 19 ]
7. Cmax (ng/mL) Multiple Dose Pharmacokinetics of Brisdelle (Paroxetine Mesylate) Capsules 7.5 mg [ Time Frame: Day 19 ]
8. Cmin (ng/mL) Multiple Dose Pharmacokinetics of Brisdelle (Paroxetine Mesylate) Capsules 7.5 mg [ Time Frame: Day 19 ]
9. Tmax (Hour) Multiple Dose Pharmacokinetics of Brisdelle (Paroxetine Mesylate) Capsules 7.5 mg [ Time Frame: Day 19 ]
10. Accumulation Index Multiple Dose Pharmacokinetics of Brisdelle (Paroxetine Mesylate) Capsules 7.5 mg at Day 19 [ Time Frame: Day 19 ]
    Accumulation Index is the ratio of AUC 0-24 after multiple doses versus a single dose. It is the increase in drug plasma concentration after multiple dosing until a steady state is reached. In this case the steady state Accumulation Index was calculated at Day 19. Accumulation Index is calculated at the end of the dosing period.
11. Fluctuation Index (%) Multiple Dose Pharmacokinetics of Brisdelle (Paroxetine Mesylate) Capsules 7.5 mg [ Time Frame: Day 19 ]
    Fluctuation Index is (Cmax-Cmin)/Cavg,ss. It is peak trough fluctuation within one dosing interval at steady state.
12. Cavg,ss (ng/mL) Multiple Dose Pharmacokinetics of Brisdelle (Paroxetine Mesylate) Capsules 7.5 mg [ Time Frame: Day 19 ]
13. Ct (ng/mL) Multiple Dose Pharmacokinetics of Brisdelle (Paroxetine Mesylate) Capsules 7.5 mg [ Time Frame: Day 19 ]
    C(t) is the measured plasma level "Concentration" of the drug at "time = t" expressed as nanograms per milliliter.

Eligibility Criteria

• Ages Eligible for Study: 40 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: Yes

Criteria

Inclusion Criteria:

Subjects who are healthy postmenopausal, non-smoking women of any race and ≥40 years of age at screening.

Exclusion Criteria:

Subjects who have a recent history or presence of glaucoma, migraines, cardiovascular, hepato-biliary, renal, gastrointestinal, neurologic, psychiatric, dermatologic, pulmonary, cerebrovascular, endocrine, hematologic, thromboembolic, immunologic disease or any other disorder which requires physician care; subjects who have existing medical conditions which might interfere with absorption, distribution, metabolism, or excretion of study medication; history of self-injurious behavior; history of clinical diagnosis of depression; or treatment for depression; history of clinical diagnosis of border-line personality disorder; presence of any of the following psychiatric disorders within the timeframes specified: Major Depressive Disorder-Lifetime; Dysthymia-Past 2 Years; Bipolar Disorder-Lifetime; Panic Disorder-Lifetime; Agoraphobia-Past Month; Social Phobia-Past Month; Obsessive Compulsive Disorder-Past Month; Generalized Anxiety-Lifetime; Psychotic Disorders-Lifetime; Anorexia Nervosa-Past 10 Years; Bulimia-Past 10 Years; Suicidality/Suicide Ideation-Lifetime; Post Traumatic Stress Disorder-Lifetime.

Subjects with a history of seizures; sitting blood pressure (BP) < 90/50 or > 150/90 mmHg; sitting heart rate (HR) < 45 or > 90 beats/min; clinical laboratory test results outside of the normal range for the laboratory conducting the test; positive urine pregnancy test at Screening or Day 0; subjects who have a history of sensitivity to active and/or inactive ingredients in Brisdelle (paroxetine mesylate) Capsules 7.5 mg; subjects who have a history of significant allergies; subjects who have a present or past history of narcotic addiction, drug abuse, or alcoholism; subjects who have smoked or used tobacco during the last 6 months; subjects who have donated one or more pints of blood within 30 days prior to treatment administration; subjects who have symptoms of any significant acute illnesses at the screening visit; subjects who used any investigational drug within 30 days prior to treatment administration; subjects who took any substances known to be Cytochrome P450 2D6 (CYP2D6) inhibitors within 14 days of study start and throughout the entire study; subjects who used any prescription medications within 14 days of the screening visit; subjects who used St John's Wort within 14 days of the screening visit; subjects who used any over the counter preparations including herbal or nutritional supplements and multivitamins within 10 days prior to receiving the first study treatment; subjects who have consumed foods or beverages containing caffeine/xanthine or alcohol; subjects who have a positive screen for hepatitis B surface antigen (HBsAg) or hepatitis C antibody; subjects who have a positive screen for the Human Immunodeficiency Virus (HIV) antibody; subjects who have a positive urine drug screen; subjects who have any clinically significant illness within 90 days prior to receiving the first dose of study medication.

Contacts and Locations

Locations

United States, Maryland

SNBL Clinical Pharmacology Center

Baltimore, Maryland, United States, 21201

Sponsors and Collaborators

Noven Therapeutics

Investigators

• Principal Investigator: Mohamed Al-Ibrahim, MD

More Information

Additional Information:

Sponsor 

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Cristina Castelli M, Bhaskar S, Lippman J. Pharmacokinetic properties of once-daily oral low-dose mesylate salt of paroxetine (LDMP 7.5 mg) following single and multiple doses in healthy postmenopausal women. Clin Ther. 2013 Jun;35(6):862-9. doi: 10.1016/j.clinthera.2013.05.001.

• Responsible Party: Noven Therapeutics
• ClinicalTrials.gov Identifier: NCT01829919
• Other Study ID Numbers: N30-005
• First Posted: April 11, 2013
• Results First Posted: February 24, 2014
• Last Update Posted: October 15, 2015
• Last Verified: October 2015

Keywords provided by Noven Therapeutics:

Menopause; Hot flashes; Vasomotor symptoms; Climacteric symptoms; perimenopause; Mesafem; Brisdelle; Low-Dose Mesylate salt of Paroxetine (LDMP)

Additional relevant MeSH terms:

Paroxetine; Serotonin Uptake Inhibitors; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Molecular Mechanisms of Pharmacological Action; Neurotransmitter Agents; Serotonin Agents; Physiological Effects of Drugs; Antidepressive Agents, Second-Generation; Antidepressive Agents; Psychotropic Drugs; Cytochrome P-450 CYP2D6 Inhibitors; Cytochrome P-450 Enzyme Inhibitors; Enzyme Inhibitors