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

Study Overview
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Brief Summary
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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.

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

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

Conditions
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Postmenopausal Symptoms

Intervention / Treatment
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* Drug: Brisdelle (paroxetine mesylate)


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 40 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Brisdelle (paroxetine mesylate)<br>Brisdelle (paroxetine mesylate) Capsules taken orally with 240 mL of water for 20 days. | Drug: Brisdelle (paroxetine mesylate)<br>* 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.<br>* Other names: LDMP (Low-Dose Mesylate salt of Paroxetine);|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Menopause, Hot flashes, Vasomotor symptoms, Climacteric symptoms, perimenopause, Mesafem, Brisdelle, Low-Dose Mesylate salt of Paroxetine (LDMP)