Noven Announces Publication of Exploratory Analyses from Pooled Phase 3 Results of the Effects of Brisdelle® (Paroxetine) Capsules on Weight and Sexual Function During Treatment of Vasomotor Symptoms Associated with Menopause

Noven Pharmaceuticals, Inc., today announced the publication of data on the effects of low-dose mesylate salt of paroxetine (LDMP), marketed as Brisdelle® (paroxetine) capsules, 7.5 mg, in the October 2014 issue of Menopause, the peer-reviewed, scientific journal of The North American Menopause Society (NAMS). The article, “Effects of low-dose paroxetine 7.5 mg on weight and sexual function during treatment of vasomotor symptoms associated with menopause,” presents exploratory analyses from pooled results that measured the impact of Brisdelle on weight and sexual function within two, double-blind, randomized, placebo-controlled Phase 3 trials of women with moderate to severe vasomotor symptoms (VMS), commonly referred to as hot flashes.

The article describes the exploratory analyses of pooled data from the two Phase 3 Brisdelle trials. The analyses showed that the frequency of treatment-emergent sexual dysfunction and weight change from baseline were similar between Brisdelle and placebo. As noted in the article, there are limitations to these analyses and it is unknown whether either might appear as an adverse event with longer term therapy. To view the full article published in Menopause please click here for article access.

“Many physicians and patients are aware of reports of sexual dysfunction and changes in body weight in patients taking selective serotonin reuptake inhibitors, and specifically paroxetine, at the higher doses used for depression and other psychiatric disorders,” said Joel Lippman, M.D., FACOG, Noven’s Executive Vice President – Product Development and Chief Medical Officer. “Noven understands this may be an important factor when considering treatment for moderate to severe hot flashes and that these analyses, with their limitations, may help provide physicians with a better understanding of Brisdelle.”

Brisdelle was specifically studied and FDA-approved to treat moderate to severe VMS associated with menopause. Brisdelle, at 7.5 mg, is a lower dose of paroxetine than that used to treat a number of psychiatric disorders. Brisdelle has not been studied in or approved for any psychiatric use.

Data collected in the 12 week and 24 week  Phase 3 studies and analyzed in the article included changes in body mass index (BMI) and weight, Arizona Sexual Experiences Scale (ASEX), Hot Flash-Related Daily Interference Scale (HFRDIS) sexuality subscore, and adverse events (AEs) related to weight or sexual dysfunction. The article includes results for each of these assessments at week 4, 12 (pooled data) and 24 (24-week study).

Percentage change in median body weight from baseline to Week 4 was 0% in the Brisdelle arm and +0.21% in the placebo arm. The change from baseline in mean body weight at week 12 was +0.17% with Brisdelle and +0.52% with placebo and at week 24 was +0.48% with Brisdelle and +0.09% with placebo. Median change from baseline in BMI and proportion of subjects with weight gain of ≥7% compared to baseline were also analyzed, and the difference between Brisdelle and placebo trended similarly.

As noted in the article, at the onset of these studies almost 60% of participants reported sexual dysfunction based on the ASEX. The proportion of participants reporting sexual dysfunction in the Brisdelle group compared to placebo at 4 weeks was 56% in both arms, 55% vs 52% at week 12, and 56% vs 57% at week 24, respectively. HFRDIS subscore results were also analyzed and the difference between Brisdelle and placebo trended similarly.

Data regarding weight gain and sexual function (as measured by ASEX) were prospectively collected in both Phase 3 clinical trials. They were not, however, primary endpoints nor pre-specified in the statistical analysis plan and the article presents exploratory analyses of pooled data. The ASEX scale has only been validated in psychiatric patients taking antidepressants. HFRDIS was a pre-specified secondary endpoint in these studies, but the sexuality subscore was evaluated separately in the analyses in this article. The HFRDIS sexuality subscore is not validated for standalone use. The article notes other limitations of the study, including that the study was not specifically designed to evaluate sexual dysfunction in VMS and that the study had a relatively short 24-week duration of treatment and follow-up.

The results of these analyses were also selected for oral presentation at the 2013 Annual Meeting of The North American Menopause Society and are publicly available on clinicaltrials.gov. The authors include: David J. Portman, M.D., Columbus Center for Women’s Health Research, Columbus, OH; Andrew M. Kaunitz, M.D.,  University of Florida College of Medicine,  Jacksonville, FL; Kazem Kazempour, Ph.D. and  Hana Mekonnen, M.A.,  Amarex Clinical Research, Germantown, M.D.;  and Sailaja Bhaskar, Ph.D. and  Joel Lippman, M.D., Noven Pharmaceuticals, Inc., New York, NY. Conflicts of interest and financial disclosures are presented below. 

About Brisdelle
Brisdelle (paroxetine) capsules, 7.5 mg, was approved by the FDA in June 2013 for the treatment of moderate to severe VMS associated with menopause, commonly referred to as hot flashes.

Brisdelle, as a treatment for moderate to severe VMS associated with menopause, was studied in one Phase 2 and two, double-blind, randomized, placebo-controlled Phase 3 trials in 1,276 women. Brisdelle has similar warnings and precautions to the higher doses of paroxetine used to treat a number of psychiatric disorders, including a Boxed Warning about Suicidal Thoughts or Behaviors. The most common adverse reactions, defined as those experienced by at least 2 percent of patients taking Brisdelle compared to placebo, were headache (6.3 vs. 4.8 percent), fatigue/malaise/lethargy (4.9 vs. 2.8 percent) and nausea/vomiting (4.3 vs. 2.3 percent).

For the full Prescribing Information, including the Medication Guide, visit www.Brisdelle.com.

INDICATION
BRISDELLE (paroxetine) capsules is a prescription medicine used to reduce moderate to severe hot flashes associated with menopause.
BRISDELLE is not approved to treat depression or any other psychiatric conditions.

IMPORTANT SAFETY INFORMATION
What is the most important information I should know about BRISDELLE?

Call your healthcare provider right away if you have any of the following symptoms, or go to the nearest emergency room:

Suicidal thoughts or actions:

  • BRISDELLE, and related antidepressant medicines, may increase suicidal thoughts or actions within the first few months of treatment.

  • Depression or other serious mental illnesses are the most important causes of suicidal thoughts or actions.

  • Watch for these changes and call your healthcare provider right away if you notice:
    • New or sudden changes in mood, behavior, actions, thoughts, or feelings, especially if severe.
    • Pay particular attention to such changes when BRISDELLE is started.

Keep all follow-up visits with your healthcare provider and call between visits if you are worried about symptoms.

Call your healthcare provider right away or go to the nearest emergency room if you have any of the following symptoms, especially if they are new, worse, or worry you:

  • Attempts to commit suicide; acting on dangerous impulses; acting aggressive or violent; thoughts about suicide or dying; new or worse depression; new or worse anxiety or panic attacks; feeling agitated, restless, angry, or irritable; trouble sleeping; an increase in activity or talking more than what is normal for you or other unusual changes in behavior or mood.

Serotonin Syndrome: This condition can be life-threatening and may include: Nervousness, hallucinations, coma, or other changes in mental status; coordination problems or small movements of the muscles that you cannot control; racing heartbeat, high or low blood pressure; sweating or fever; nausea, vomiting, or diarrhea; muscle rigidity; dizziness; flushing; tremors; seizures.

Reduced effectiveness of tamoxifen: Tamoxifen (a medicine used to treat breast cancer) may not work as well if it is taken at the same time as BRISDELLE. If you are taking tamoxifen, tell your healthcare provider before starting BRISDELLE.

Abnormal bleeding: BRISDELLE may increase your risk of bleeding or bruising, especially if you take the blood thinner warfarin, or non-steroidal anti-inflammatory drugs (NSAIDs), like ibuprofen, naproxen, or aspirin.

Low salt (sodium) levels in the blood: Elderly people may be at greater risk for this. Symptoms may include: headache; weakness or feeling unsteady; confusion, problems concentrating or thinking or memory problems.

Bone Fractures: Women who take BRISDELLE may have a higher risk of bone fractures.

Manic episodes: Greatly increased energy; severe trouble sleeping; racing thoughts; reckless behavior; unusually grand ideas; excessive happiness or irritability; talking more or faster than usual.

Seizures or convulsions.

Restlessness: Women who take BRISDELLE may feel an inner restlessness, nervousness, or be unable to sit still or stand still especially when they start taking BRISDELLE.

Visual symptoms.

Who should not take BRISDELLE?
Do not take BRISDELLE if you:

  • Take a Monoamine Oxidase Inhibitor (MAOI). Ask your healthcare provider or pharmacist if you are not sure if you take an MAOI, including the antibiotic linezolid.
    • Do not take an MAOI within 14 days of stopping BRISDELLE unless directed to do so by your healthcare provider.
    • Do not start BRISDELLE if you stopped taking an MAOI in the last 14 days unless directed to do so by your healthcare provider.
    • People who take BRISDELLE close in time to an MAOI may have serious or life-threatening side effects. Get medical help right away if you have any of these symptoms:
      • High fever, uncontrolled muscle spasms, stiff muscles, rapid changes in heart rate or blood pressure, confusion, loss of consciousness (pass out).
  • Take thioridazine or pimozide. Do not take thioridazine or pimozide together with BRISDELLE because this can cause serious heart problems or sudden death.
  • Are allergic to paroxetine or any of the ingredients in BRISDELLE.
  • Are pregnant. BRISDELLE is not for pregnant women. Paroxetine can harm your unborn baby.

What should I tell my healthcare provider before starting BRISDELLE?
Before starting BRISDELLE, tell your healthcare provider if you:

  • Have liver or kidney problems; bipolar disorder or mania; low sodium levels in your blood; glaucoma (high pressure in the eye); have or had seizures, convulsions, or bleeding problems; have any other medical conditions; are breastfeeding or plan to breastfeed.

Tell your healthcare provider about all the medicines that you take, including prescription and non-prescription medicines such as migraine headache medication (triptans), other antidepressants and antipsychotics, vitamins, and herbal supplements. 

If you take BRISDELLE, you should not take any other medicines that contain paroxetine, including Paxil®, Paxil CR®, and Pexeva®.

What should I avoid while taking BRISDELLE?
You should not drive, operate heavy machinery, or do other dangerous activities until you know how BRISDELLE affects you. 

What are the most common side effects of BRISDELLE?
The most common possible side effects of BRISDELLE include: headache; tiredness; nausea and vomiting.

Tell your healthcare provider if you have any side effect that bothers you or does not go away. These are not all the possible side effects of BRISDELLE. 

Please read the Medication Guide within the full Prescribing Information before taking BRISDELLE. Call your doctor for medical advice about side effects. You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch or call 1-800-FDA-1088.

About Menopause
During perimenopause, the transition period before a woman reaches menopause, estrogen levels gradually decline and periods may become irregular. Natural menopause is typically confirmed when a woman has missed her menstrual periods for 12 consecutive months. The average age of a woman entering natural menopause is 51 years old. Some women may undergo surgical menopause, which can take place at any age. Surgical menopause occurs when both ovaries are surgically removed (called an oophorectomy), often along with the uterus (called a hysterectomy). Because ovaries are the body’s main source of estrogen production, a woman enters menopause when they are removed. The severity of symptoms associated with menopause varies from woman to woman. Hot flashes are the most common symptom of menopause. Because the journey is unique for each woman, it is important for women going through menopause to have a thorough discussion about the transition with their doctors and determine if treatment is appropriate.

Disclosures
The studies presented in the article were funded by Noven Pharmaceuticals, Inc.

Dr. Portman is a member of the board of the International Society for the Study of
Women’s Sexual Health. Dr. Portman has served or is serving as a consultant
to Meda Pharmaceuticals, Inc. (Somerset, NJ), Noven Pharmaceuticals, Inc. (New York, NY), and Pfizer Pharmaceuticals, Inc. (New York, NY). The Columbus Center for
Women’s Health Research has received fees for his participation in speakers’ bureaus on behalf of Noven Pharmaceuticals, Inc., Teva Pharmaceutical Industries, Ltd. (Jerusalem, Israel), and Warner Chilcott (Rockaway, NJ). The Columbus Center for Women’s Health Research has received research/grant support from Bayer Corporation (Perkasie, PA), Depomed, Inc. (Menlo Park, CA), Noven Pharmaceuticals, Inc., Pfizer, Inc., and Teva Pharmaceutical Industries, Ltd. Dr. Portman has received fees from Noven Pharmaceuticals, Inc., for participation in review activities and for the development of an educational presentation on hormone therapy.

Dr. Andrew M. Kaunitz is a member of the board of the NAMS (Mayfield Heights, OH). He has received consultancy fees from Depomed, Inc. and receives consultancy fees from Merck (Whitehouse Station, NJ), Bayer AG (Leverkusen, Germany), Teva Pharmaceuticals, Ltd., and Actavis, Inc. (Parsippany, NJ). The Department of Obstetrics and Gynecology, University of Florida College of Medicine, Jacksonville, is the recipient of grants from Bayer AG, EndoCeutics, Inc. (Quebec, Canada), Noven Pharmaceuticals, Inc., Teva Pharmaceutical Industries, Ltd. and Trimel Pharmaceuticals (Toronto, Canada).

Dr. Kazem Kazempour and Ms. Hana Mekonnen provided statistical services to Noven.

Dr. Sailaja Bhaskar and Dr. Joel Lippman are employees of Noven Pharmaceuticals, Inc.

Brisdelle and Pexeva are registered trademarks of Noven Therapeutics, LLC. All other registered trademarks are the property of their respective owners.

About Noven
Noven Pharmaceuticals, Inc. is a specialty pharmaceutical company engaged in the research, development, manufacturing, marketing and sale of prescription pharmaceutical products. Noven is committed to developing and offering products and technologies that meaningfully benefit patients, its customers and its industry partners, with a commercial focus on treatment options for women experiencing menopausal vasomotor symptoms. For more information about Noven, visit www.noven.com.

Contacts:
Joseph C. Jones
Vice President – Corporate Affairs
Noven Pharmaceuticals, Inc.
305-253-1916

Samantha Schwarz
Executive Director
Golin
312-729-4370