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

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

• Brisdelle (paroxetine mesylate) (Drug), also known as Former Names: Mesafem capsules 7.5 mg or, LDMP (Low-Dose Mesylate salt of Paroxetine): 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.

Primary outcomes

• 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 [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.
• Fluctuation Index (%) Multiple Dose Pharmacokinetics of Brisdelle (Paroxetine Mesylate) Capsules 7.5 mg [Day 19]: Fluctuation Index is (Cmax-Cmin)/Cavg,ss. It is peak trough fluctuation within one dosing interval at steady state.
• 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 [Day 19]: C(t) is the measured plasma level "Concentration" of the drug at "time = t" expressed as nanograms per milliliter.

Sex: Female, ages: 40 Years to any, accepts healthy volunteers

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.

Participant flow

Outcome results

• AUC (Hour*ng/mL) Single Dose Pharmacokinetics of Brisdelle™ (Paroxetine Mesylate) Capsules 7.5 mg (Primary), Mean, Hour*ng/mL: Brisdelle (Paroxetine Mesylate) Capsules 7.5 mg 86.95 +/- 166.19
• Cmax (ng/mL) Single Dose Pharmacokinetics of Brisdelle™ (Paroxetine Mesylate) Capsules 7.5 mg (Primary), Mean, ng/mL: Brisdelle (Paroxetine Mesylate) Capsules 7.5 mg 2.77 +/- 3.38
• Kel (Hour^-1) Single Dose Pharmacokinetics of Brisdelle™ (Paroxetine Mesylate) Capsules 7.5 mg (Primary), Mean, Hour^(-1): Brisdelle (Paroxetine Mesylate) Capsules 7.5 mg 0.05 +/- 0.01
• Mean t1/2 Single Dose Pharmacokinetics of Brisdelle™ (Paroxetine Mesylate) Capsules 7.5 mg (Primary), Mean, Hours: Brisdelle (Paroxetine Mesylate) Capsules 7.5 mg 17.30 +/- 11.45
• Median t1/2 Single Dose Pharmacokinetics of Brisdelle (Paroxetine Mesylate) Capsules 7.5 mg (Primary), Median, hours: Brisdelle (Paroxetine Mesylate) Capsules 7.5 mg 6.00 (1.00 to 8.00)
• AUC (Hour*ng/mL) Multiple Dose Pharmacokinetics of Brisdelle (Paroxetine Mesylate) Capsules 7.5 mg (Primary), Mean, Hour*ng/mL: Brisdelle (Paroxetine Mesylate) Capsules 7.5 mg 237.34 +/- 222.65
• Cmax (ng/mL) Multiple Dose Pharmacokinetics of Brisdelle (Paroxetine Mesylate) Capsules 7.5 mg (Primary), Mean, ng/mL: Brisdelle (Paroxetine Mesylate) Capsules 7.5 mg 13.10 +/- 11.92
• Cmin (ng/mL) Multiple Dose Pharmacokinetics of Brisdelle (Paroxetine Mesylate) Capsules 7.5 mg (Primary), Mean, ng/mL: Brisdelle (Paroxetine Mesylate) Capsules 7.5 mg 7.67 +/- 7.57
• Tmax (Hour) Multiple Dose Pharmacokinetics of Brisdelle (Paroxetine Mesylate) Capsules 7.5 mg (Primary), Mean, Hours: Brisdelle (Paroxetine Mesylate) Capsules 7.5 mg 6.00 (3.00 to 8.00)
• Accumulation Index Multiple Dose Pharmacokinetics of Brisdelle (Paroxetine Mesylate) Capsules 7.5 mg at Day 19 (Primary), Mean, Ratio: Brisdelle (Paroxetine Mesylate) Capsules 7.5 mg 9.71 (0.12 to 23.48)
• Fluctuation Index (%) Multiple Dose Pharmacokinetics of Brisdelle (Paroxetine Mesylate) Capsules 7.5 mg (Primary), Mean, Percentage of steady state concentration: Brisdelle (Paroxetine Mesylate) Capsules 7.5 mg 75.76 (35.57 to 153.20)
• Cavg,ss (ng/mL) Multiple Dose Pharmacokinetics of Brisdelle (Paroxetine Mesylate) Capsules 7.5 mg (Primary), Mean, ng/mL: Brisdelle (Paroxetine Mesylate) Capsules 7.5 mg 9.89 +/- 9.28
• Ct (ng/mL) Multiple Dose Pharmacokinetics of Brisdelle (Paroxetine Mesylate) Capsules 7.5 mg (Primary), Mean, ng/mL: Brisdelle (Paroxetine Mesylate) Capsules 7.5 mg 8.53 +/- 9.17

Adverse events

Time frame: 21 days

Other adverse events by term

• Results publication: 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. PMID 23795577

• Mohamed Al-Ibrahim, MD, Principal investigator