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

Evaluation of Pharmacokinetics of Paroxetine Following Single and Repeat Oral Administration of Mesafem (7.5 mg Paroxetine Mesylate) Capsules in Healthy Postmenopausal Women

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.

Study Overview

• Status: Completed
• Conditions: Postmenopausal Symptoms
• Intervention / Treatment: Drug: Brisdelle (paroxetine mesylate)

Detailed Description

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

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • SNBL Clinical Pharmacology Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 38 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / 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: LDMP (Low-Dose Mesylate salt of Paroxetine); Former Names: Mesafem capsules 7.5 mg or

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
AUC (Hour*ng/mL) Single Dose Pharmacokinetics of Brisdelle™ (Paroxetine Mesylate) Capsules 7.5 mg		Day 1
Cmax (ng/mL) Single Dose Pharmacokinetics of Brisdelle™ (Paroxetine Mesylate) Capsules 7.5 mg		Day 1
Kel (Hour^-1) Single Dose Pharmacokinetics of Brisdelle™ (Paroxetine Mesylate) Capsules 7.5 mg		Day 1
Mean t1/2 Single Dose Pharmacokinetics of Brisdelle™ (Paroxetine Mesylate) Capsules 7.5 mg		Day 1
Median t1/2 Single Dose Pharmacokinetics of Brisdelle (Paroxetine Mesylate) Capsules 7.5 mg		Day 1
AUC (Hour*ng/mL) Multiple Dose Pharmacokinetics of Brisdelle (Paroxetine Mesylate) Capsules 7.5 mg		Day 19
Cmax (ng/mL) Multiple Dose Pharmacokinetics of Brisdelle (Paroxetine Mesylate) Capsules 7.5 mg		Day 19
Cmin (ng/mL) Multiple Dose Pharmacokinetics of Brisdelle (Paroxetine Mesylate) Capsules 7.5 mg		Day 19
Tmax (Hour) Multiple Dose Pharmacokinetics of Brisdelle (Paroxetine Mesylate) Capsules 7.5 mg		Day 19
Accumulation Index Multiple Dose Pharmacokinetics of Brisdelle (Paroxetine Mesylate) Capsules 7.5 mg at 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.	Day 19
Fluctuation Index (%) Multiple Dose Pharmacokinetics of Brisdelle (Paroxetine Mesylate) Capsules 7.5 mg	Fluctuation Index is (Cmax-Cmin)/Cavg,ss. It is peak trough fluctuation within one dosing interval at steady state.	Day 19
Cavg,ss (ng/mL) Multiple Dose Pharmacokinetics of Brisdelle (Paroxetine Mesylate) Capsules 7.5 mg		Day 19
Ct (ng/mL) Multiple Dose Pharmacokinetics of Brisdelle (Paroxetine Mesylate) Capsules 7.5 mg	C(t) is the measured plasma level "Concentration" of the drug at "time = t" expressed as nanograms per milliliter.	Day 19

Collaborators and Investigators

• Sponsor: Noven Therapeutics
• Investigators: Principal Investigator: Mohamed Al-Ibrahim, MD

Publications and helpful links

General Publications

• 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.

Helpful Links

• Sponsor

Study record dates

Study Major Dates

• Study Start: July 1, 2011
• Primary Completion (Actual): August 1, 2011
• Study Completion (Actual): August 1, 2011

Study Registration Dates

• First Submitted: April 9, 2013
• First Submitted That Met QC Criteria: April 9, 2013
• First Posted (Estimate): April 11, 2013

Study Record Updates

• Last Update Posted (Estimate): October 15, 2015
• Last Update Submitted That Met QC Criteria: October 14, 2015
• Last Verified: October 1, 2015

More Information

Terms related to this study

• Keywords: Hot flashes; Menopause; Mesafem; Low-Dose Mesylate salt of Paroxetine (LDMP); perimenopause; Vasomotor symptoms; Climacteric symptoms; Brisdelle
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Psychotropic Drugs; Serotonin Uptake Inhibitors; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Serotonin Agents; Antidepressive Agents; Cytochrome P-450 Enzyme Inhibitors; Antidepressive Agents, Second-Generation; Cytochrome P-450 CYP2D6 Inhibitors; Paroxetine
• Other Study ID Numbers: N30-005