CLINICAL TRIALS

ADDYI IS PROVEN
SAFE AND EFFECTIVE

CLINICAL TRIALS

ADDYI IS PROVEN SAFE AND EFFECTIVE

Satisfying Sexual Events | Desire | Distress | Safety | Additional Findings

IN CLINICAL TRIALS, 3 ENDPOINTS WERE MET2

The efficacy of Addyi was established in three 24-week, randomized, double-blind, placebo-controlled trials in premenopausal women with acquired, generalized HSDD. Participants were age 19-55 years (mean 36 years) with an average HSDD and relationship duration of 5 years and 11 years, respectively. Approximately 40% subjects were also taking hormonal contraceptives. Women in these trials were treated with Addyi 100mg (n=1187) once-daily at bedtime, or placebo (n=1188).

SSEs = satisfying sexual events; FSFI-D = Female Sexual Function Index – Desire Domain; FSDS-R = Female Sexual Distress Scale-Revised Question 13

IN CLINICAL TRIALS, 3 ENDPOINTS WERE MET2

The efficacy of Addyi was established in three 24-week, randomized, double-blind, placebo-controlled trials in premenopausal women with acquired, generalized HSDD. Participants were age 19-55 years (mean 36 years) with an average HSDD and relationship duration of 5 years and 11 years, respectively. Approximately 40% subjects were also taking hormonal contraceptives. Women in these trials were treated with Addyi 100mg (n=1187) once-daily at bedtime, or placebo (n=1188).

SSEs = satisfying sexual events; FSFI-D = Female Sexual Function Index – Desire Domain; FSDS-R = Female Sexual Distress Scale-Revised Question 13

CLINICAL TRIAL EFFICACY

INCREASED SATISFYING SEXUAL EVENTS

Satisfying Sexual Events (SSEs)2-5

  • Studies 1, 2, and 3 measured number of monthly SSEs as a co-primary endpoint
  • SSEs included sexual intercourse, oral sex, masturbation, or genital stimulation by a partner
  • SSEs began to increase between weeks 4 and 8 and the improvement was sustained through week 24

INCREASED SEXUAL DESIRE

Sexual Desire – Measured Using Female Sexual Function Index Desire (FSFI-D) Domain2-5

  • FSFI-Desire domain was a co-primary endpoint in Study 3, and secondary endpoint in Studies 1 and 2
    • The FSFI-D consists of 2 questions: “Over the past 4 weeks, how often did you feel sexual desire or interest?” and “Over the past 4 weeks, how would you rate your level of sexual desire or interest?”6,7
    • A score of ≤3 may indicate the presence of HSDD6,7
    • Sexual desire began to increase between weeks 4 and 8 and the improvement was sustained through week 24

Sexual Desire – Measured Using E-Diary2

  • Studies 1 and 2 measured desire using eDiary scores as a co-primary endpoint
    • Every day, patients rated their level of sexual desire from a scale of 0 to 3
    • The eDiary responses were summed over a 28-day period to yield the calculated monthly sexual desire score, which ranged from 0 to 84
    • P value not reported for secondary endpoints because the trial failed on the eDiary desire co-primary efficacy endpoint

REDUCED DISTRESS ASSOCIATED WITH LOW SEXUAL DESIRE

Distress – Measured Using the Female Sexual Distress Scale-Revised, Question 13 (FSDS-R, Q13)2-5

  • Studies 1, 2, and 3 measured the decrease in distress with the FSDS-R, Q13 as a secondary endpoint
  • The FSDS-R, Q13 measures distress based on the question, “How often did you feel bothered by low sexual desire?”
  • Distress with associated low desire began to decrease between weeks 4 and 8 and the improvement was sustained through week 24

CLINICAL TRIAL SAFETY PROFILE2

ADVERSE REACTIONS LEADING TO DISCONTINUATION

The discontinuation rate due to adverse reactions was 13% among patients treated with 100mg Addyi at bedtime and 6% among patients treated with placebo. Adverse reactions** leading to discontinuation in 4 randomized, double-blind, placebo-controlled trials in premenopausal women with HSDD are shown below.

**Adverse reactions leading to discontinuation of ≥ 1% of patients receiving 100 mg Addyi at bedtime and at a higher incidence than placebo-treated patients.

MOST COMMON ADVERSE REACTIONS

Common adverse reactions† in 4 randomized, double-blind, placebo-controlled trials in premenopausal women with HSDD. The majority of these adverse reactions began within the first 14 days of treatment.

† Adverse reactions reported in ≥ 2% of patients receiving 100 mg Addyi at bedtime and at a higher incidence than placebo-treated patients.

CLINICAL TRIAL SAFETY PROFILE2

ADVERSE REACTIONS LEADING TO DISCONTINUATION

The discontinuation rate due to adverse reactions was 13% among patients treated with 100mg Addyi at bedtime and 6% among patients treated with placebo. Adverse reactions** leading to discontinuation in 4 randomized, double-blind, placebo-controlled trials in premenopausal women with HSDD are shown below.

**Adverse reactions leading to discontinuation of ≥ 1% of patients receiving 100 mg Addyi at bedtime and at a higher incidence than placebo-treated patients.

MOST COMMON ADVERSE REACTIONS

Common adverse reactions† in 4 randomized, double-blind, placebo-controlled trials in premenopausal women with HSDD. The majority of these adverse reactions began within the first 14 days of treatment.

† Adverse reactions reported in ≥ 2% of patients receiving 100 mg Addyi at bedtime and at a higher incidence than placebo-treated patients.

ADDITIONAL FINDINGS

 

POST HOC ANALYSIS OF FEMALE SEXUAL FUNCTION INDEX (FSFI)8

Post hoc analyses of FSFI total and individual domain data were pooled from 3 pivotal, multicenter, randomized, placebo-controlled, double-blind trials in premenopausal women with HSDD who received flibanserin (n=1165) or placebo (n=1204). Addyi has not been studied for the treatment of any female sexual dysfunction other than acquired, generalized HSDD.

additionalfindings

Post Hoc Analysis of FSFI Domain Scores ‡

  • FSFI total and individual domain data were pooled from 3 pivotal, multicenter, randomized, placebo-controlled, double-blind trials in premenopausal women with HSDD who received flibanserin (n=1165) or placebo (n=1204)
  • Post-hoc exploratory analyses compared change from baseline in FSFI scores of flibanserin and placebo groups at each assessment time point by t-test
    • FSFI questionnaire was administered at baseline and Weeks 4,8,16, and 24
    • There was no adjustment for multiple comparisons
    • Missing data were handled using the last observation carried forward (LOCF) method
‡Post hoc analysis sponsored by Sprout.

ADDITIONAL FINDINGS

 

POST HOC ANALYSIS OF FEMALE SEXUAL FUNCTION INDEX (FSFI)8

Post hoc analyses of FSFI total and individual domain data were pooled from 3 pivotal, multicenter, randomized, placebo-controlled, double-blind trials in premenopausal women with HSDD who received flibanserin (n=1165) or placebo (n=1204). Addyi has not been studied for the treatment of any female sexual dysfunction other than acquired, generalized HSDD.

POST HOC ANALYSIS OF FEMALE SEXUAL FUNCTION INDEX (FSFI)

Post Hoc Analysis of FSFI Domain Scores ‡

  • FSFI total and individual domain data were pooled from 3 pivotal, multicenter, randomized, placebo-controlled, double-blind trials in premenopausal women with HSDD who received flibanserin (n=1165) or placebo (n=1204)
  • Post-hoc exploratory analyses compared change from baseline in FSFI scores of flibanserin and placebo groups at each assessment time point by t-test
    • FSFI questionnaire was administered at baseline and Weeks 4,8,16, and 24
    • There was no adjustment for multiple comparisons
    • Missing data were handled using the last observation carried forward (LOCF) method
‡Post hoc analysis sponsored by Sprout.

POST HOC ANALYSIS OF EFFECT ON WEIGHT9

Post hoc analysis of pooled data from 3 pivotal, multicenter, randomized, placebo-controlled, double-blind trials in premenopausal women with HSDD who received flibanserin. Addyi is not indicated for weight loss.

Post Hoc Analysis of Pooled Data from 3 Clinical Trials in Premenopausal Women with HSDD

  • Mean baseline weight was ~73kg (~160lbs)
  • Weight gain ≥7% at 24 weeks occurred in 1.8% women receiving flibanserin and 3.4% women receiving placebo
  • Higher baseline BMI was associated with greater weight loss.
  • No association seen between effect on weight and treatment response, contraceptive use, smoking status, SSRI/SNRI use, or occurrence of nausea
  • Body weight was measured to assess weight loss and weight gain as potential adverse events
  • Study was not designed to evaluate weight loss. Patients were not selected based on obesity status nor did they enter the studies with the goal of losing weight.

COADMINISTRATION WITH SSRI/SNRI

Clinical considerations for taking Addyi with SSRIs and SNRIs

Information based on pharmacologic action of products based on respective Prescribing Information as of May 2021. All product names, trademarks and registered trademarks are property of their respective owners.

COADMINISTRATION WITH SSRI/SNRI

Clinical considerations for taking Addyi with SSRIs and SNRIs

Information based on pharmacologic action of products based on respective Prescribing Information as of May 2021. All product names, trademarks and registered trademarks are property of their respective owners.

SAFETY STUDY WITH SSRI/SNRI11

12 week randomized, double-blind, placebo-controlled clinical trial in 111 premenopausal women with mild to remitted depression treated with a stable dose of SSRI/SNRI* and symptoms of HSDD.**

  • Overall, no increased risk of adverse events, including depression and anxiety were observed
  • No instances of suicidality (C-SSRS)
  • AEs ≥3% with Addyi and higher than placebo: dry mouth, insomnia, back pain, dizziness
  • This study was designed to assess flibanserin safety; No conclusions regarding efficacy can be made
*citalopram, escitalopram, fluoxetine, paroxetine, sertraline, desvenlafaxine, duloxetine, venlafaxine
**Planned sample size was 200 patients; study was terminated early due to commercial reasons
†Includes 28 patients on fixed 100 mg qhs dose and 45 patients on up-titrated dose (50 mg qhs first two weeks, followed by 100 mg qhs) C-SSRS = Columbia-Suicide Severity Rating Scale; QIDS-SR16 = 16-item Quick Inventory of Depressive Symptomology-Self Report

CONTACT US

GENERAL:
844-PINK-PILL (844-746-5745)
info@sproutpharma.com

MEDICAL INFO:
844-746-5745 x 3
medicalaffairs@sproutpharma.com

ADDYI PREGNANCY EXPOSURE REGISTRY:
844-746-5745 x 2

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Indication and Important Safety Information including Boxed Warning regarding hypotension and syncope in certain settings

WARNING: HYPOTENSION AND SYNCOPE IN CERTAIN SETTINGS
See full prescribing information for complete boxed warning.

  • Use of ADDYI and alcohol together close in time increases the risk of severe hypotension and syncope. 

Important Safety Information including Boxed Warning regarding hypotension and syncope in certain settings

WARNING: HYPOTENSION AND SYNCOPE IN CERTAIN SETTINGS

See full prescribing information for complete boxed warning.

  • Use of ADDYI and alcohol together close in time increases the risk of severe hypotension and syncope.  Counsel patients to wait at least two hours after consuming one or two standard alcoholic drinks before taking ADDYI at bedtime or to skip their ADDYI dose if they have consumed three or more standard alcoholic drinks that evening.
  • Severe hypotension and syncope can occur when ADDYI is used with moderate or strong CYP3A4 inhibitors or in patients with hepatic impairment; therefore, ADDYI use in these settings is contraindicated.

Contraindications

  • Moderate or strong cytochrome P450 3A4 (CYP3A4) inhibitors
  • Hepatic impairment
  • Known hypersensitivity to ADDYI or any of its components. Reactions, including anaphylaxis, reactions consistent with angioedema, pruritus, and urticaria have been reported. 

Warnings and Precautions

  • Hypotension and Syncope Due to an Interaction with Alcohol:  Taking ADDYI within two hours after consuming alcohol increases the risk of severe hypotension and syncope. To reduce this risk, counsel patients to wait at least two hours after drinking one or two standard alcoholic drinks before taking ADDYI at bedtime. Patients who drink three or more standard alcoholic drinks should skip their ADDYI dose that evening. After taking ADDYI at bedtime, advise patients to not use alcohol until the following day.
  • Hypotension and Syncope with CYP3A4 Inhibitors: Moderate or strong CYP3A4 inhibitors significantly increase ADDYI concentrations, which can lead to hypotension and syncope. Concomitant use of ADDYI with a moderate or strong CYP3A4 inhibitor is contraindicated. Concomitant use of multiple weak CYP3A4 inhibitors that may include herbal supplements (e.g., ginkgo, resveratrol) or non-prescription drugs (e.g., cimetidine) could also lead to clinically relevant increases in flibanserin concentrations that may increase the risk of hypotension and syncope.
  • Central Nervous System (CNS) Depression (e.g., Somnolence, Sedation):  Can occur with ADDYI alone and is exacerbated by other CNS depressants including alcohol, and in settings where flibanserin concentrations are increased such as CYP3A4 inhibitors. The risk of CNS depression is also increased if ADDYI is taken during waking hours. Patients should avoid activities requiring full alertness (e.g., operating machinery or driving) until at least six hours after each dose and until they know how ADDYI affects them.
  • Hypotension and Syncope with ADDYI Alone:  The use of ADDYI – without other concomitant medications known to cause hypotension or syncope – can cause hypotension and syncope. The risk of hypotension and syncope is increased if ADDYI is taken during waking hours or if higher than the recommend dose is taken. Consider the benefits of ADDYI and the risks of hypotension and syncope in patients with pre-existing conditions that predispose to hypotension. Patients with pre-syncope should immediately lie supine and promptly seek medical help if symptoms do not resolve. Prompt medical attention should also be obtained for patients who experience syncope.
  • Syncope and Hypotension in Patients with Hepatic Impairment: Any degree of hepatic impairment significantly increases flibanserin concentrations, which can lead to hypotension and syncope. ADDYI is contraindicated in patients with hepatic impairment.
  • Hypersensitivity Reactions: Reactions including anaphylaxis, reactions consistent with angioedema, pruritus, and urticaria have been reported with ADDYI. Immediately discontinue ADDYI and initiate appropriate treatment if hypersensitivity reaction occurs. 

Drug Interactions

  • Alcohol: coadministration of ADDYI with alcohol increased the risk of hypotension, syncope, and CNS depression compared to the use of ADDYI alone or alcohol alone. Patients should wait at least two hours after consuming one or two standard alcoholic drinks before taking ADDYI at bedtime or to skip their ADDYI dose if they have consumed three or more alcoholic drinks that evening.
  • CNS Depressants: (i.e., diphenhydramine, opioids, hypnotics, benzodiazepines, etc.) Concomitant use with ADDYI may increase the risk of CNS depression compared to use of ADDYI alone.
  • Moderate or Strong CYP3A4 Inhibitors: ADDYI is contraindicated in women taking moderate (e.g., fluconazole, etc.) or strong (e.g., ketoconazole, etc.) CYP3A4 inhibitors
  • Oral Contraceptives and Other Weak CYP3A4 Inhibitors:  In combination with ADDYI may increase the risk of adverse reactions
  • Strong CYP2C19 Inhibitors: (i.e., proton pump inhibitors, SSRI’s, benzodiazepines, antifungals, etc.) Increase flibanserin exposure which may increase risk of hypotension, syncope, and CNS depression
  • CYP3A4 Inducers: (i.e., carbamazepine, phenobarbital, etc.) Concomitant use substantially decreases flibanserin exposure compared to the use of ADDYI alone and is not recommended.
  • Digoxin or other P-glycoprotein (P-gp) substrates:  Increases digoxin concentration, which may lead to digoxin toxicity. Increase monitoring of drugs transported by P-gp that have a narrow therapeutic index.

Most Common Adverse Reactions

  • Most common adverse reactions (ADDYI incidence ≥2% and higher than placebo) are dizziness, somnolence, nausea, fatigue, insomnia, and dry mouth.

See Full Prescribing Information and Medication Guide, including Boxed Warning regarding hypotension and syncope in certain settings at addyi.com/pi.

 

Indication

ADDYI (flibanserin) is indicated for the treatment of premenopausal women with acquired, generalized hypoactive sexual desire disorder (HSDD) as characterized by low sexual desire that causes marked distress or interpersonal difficulty and is NOT due to:

  • A co-existing medical or psychiatric condition,
  • Problems within the relationship, or
  • The effects of a medication or other drug substance.

Acquired HSDD refers to HSDD that develops in a patient who previously had no problem with sexual desire. Generalized HSDD refers to HSDD that occurs regardless of the type of stimulation, situation, or partner.

Limitations of Use:

  • ADDYI is not indicated for the treatment of HSDD in postmenopausal women or in men.
  • ADDYI is not indicated to enhance sexual performance.

PRIVACY POLICY | LEGAL NOTICE

This site is intended for residents of the United States.
Addyi is a registered trademark of Sprout Pharmaceuticals, Inc. or its affiliates. All other trademarks are the property of their respective owners.
© 2022 Sprout Pharmaceuticals, Inc. US–1900020.19

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1. IQVIA Monthly Total Prescriptions Volume Data Comparing Addyi vs Vyleesi in the US. September 2021.
2. Addyi Prescribing Information.
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6. Gerstenberger EP, Rosen RC, Brewer JV, et al. Sexual desire and the Female Sexual Function Index (FSFI): a sexual desire cutpoint for clinical interpretation of the FSFI in women with and without hypoactive sexual desire disorder. J Sex Med. 2010;7(9):3096–3103.
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8. Simon JA, Millheiser L, Clayton AH, et al. Improvements in Female Sexual Function Index (FSFI) domains over time after flibanserin treatment in premenopausal women with hypoactive sexual desire disorder (HSDD). Poster presented at the International Society for the Study of Women’s Sexual Health (ISSWSH) 2020 Annual Meeting; March 5-8, 2020; Orlando, FL.(A084).
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10. https://www.fda.gov/drugs/drug-interactions-labeling/drug-development-and-drug-interactions-table-substrates-inhibitors-and-inducers
11. Clayton AH, Harry AC, Yuan J, et al. Safety of flibanserin in women treated with antidepressants: A randomized, placebo-controlled study. J Sex Med 2018;15(1):43-51.
12. Stahl SM, et al. Mechanism of action of flibanserin, a multifunctional serotonin agonist and antagonist (MSAA), in hypoactive sexual desire disorder, CNS Spectrums. 2015;20:1-6.
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16. Millheiser L, Clayton AH, Parish SJ, et al. Safety and tolerability of evening ethanol consumption and bedtime administration of flibanserin in healthy premenopausal female subjects. Sex Med 2019;7:418-424. https://www.smoa.jsexmed.org/article/S2050-1161(19)30127-8/abstract
17. Arnow BA, Millheiser L, Garrett A et al. Women with hypoactive sexual desire disorder compared to normal females: a functional magnetic resonance imaging study. Neuroscience 2009;158:484-502.
18. Woodard TL, Nowak NT, Balon R et al. Brain activation patterns in women with acquired hypoactive sexual desire disorder and women with normal sexual function: a cross-sectional pilot study. Fertil Steril 2013;100:1068-1076.
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20. Holstege G. How the emotional motor system controls the pelvic organs. Sex Med Rev. 2016: 4;303-328.
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