TY - JOUR
T1 - Responder Analyses from a Phase 2b Dose-Ranging Study of Bremelanotide
AU - Althof, Stanley
AU - Derogatis, Leonard R.
AU - Greenberg, S.
AU - Clayton, Anita H.
AU - Jordan, Robert
AU - Lucas, J.
AU - Spana, Carl
N1 - Funding Information:
Funding: This study was sponsored by Palatin Technologies, the innovator of bremelanotide.
Funding Information:
Conflicts of interest: Stanley Althof has received research support or consulting fees from AMAG Pharmaceuticals, Clinical Outcome Solutions, Endoceutics, Ixchelsis, Palatin Technologies, Sprout Pharmaceuticals, Strategic Science Technologies, and Valeant. Leonard R. Derogatis has received research support or consulting fees from AMAG Pharmaceuticals and Palatin Technologies. Sally Greenberg has received research support or consulting fees from Palatin Technologies. Anita H. Clayton has received royalties from Ballantine Books/Random House, Changes in Sexual Functioning Questionnaire, and Guilford Publications; has received research support or consulting fees from Alkermes, AMAG Pharmaceuticals, Endoceutics, Fabre-Kramer, Ivix, Janssen, Palatin Technologies, Sage Therapeutics, S1 Biopharma, Sprout, Takeda, and Valeant Pharmaceuticals; and has stocks, stock options, or ownership interest, excluding diversified mutual funds, in Euthymics and S1 Biopharma. Robert Jordan, Johna Lucas, and Carl Spana are employees and stockholders of Palatin Technologies.We thank Linnéa Elliott and Maria Vinall of The Curry Rockefeller Group for editorial assistance (funded by Palatin Technologies). Additional editorial support in the preparation of this manuscript was provided by Phase Five Communications, funded by AMAG Pharmaceuticals, the licensee of bremelanotide. The authors are responsible for all content and editorial decisions, and received no honoraria related to the development of this manuscript. Conflicts of interest: Stanley Althof has received research support or consulting fees from AMAG Pharmaceuticals, Clinical Outcome Solutions, Endoceutics, Ixchelsis, Palatin Technologies, Sprout Pharmaceuticals, Strategic Science Technologies, and Valeant. Leonard R. Derogatis has received research support or consulting fees from AMAG Pharmaceuticals and Palatin Technologies. Sally Greenberg has received research support or consulting fees from Palatin Technologies. Anita H. Clayton has received royalties from Ballantine Books/Random House, Changes in Sexual Functioning Questionnaire, and Guilford Publications; has received research support or consulting fees from Alkermes, AMAG Pharmaceuticals, Endoceutics, Fabre-Kramer, Ivix, Janssen, Palatin Technologies, Sage Therapeutics, S1 Biopharma, Sprout, Takeda, and Valeant Pharmaceuticals; and has stocks, stock options, or ownership interest, excluding diversified mutual funds, in Euthymics and S1 Biopharma. Robert Jordan, Johna Lucas, and Carl Spana are employees and stockholders of Palatin Technologies. Funding: This study was sponsored by Palatin Technologies, the innovator of bremelanotide.
Funding Information:
Conflicts of interest: Stanley Althof has received research support or consulting fees from AMAG Pharmaceuticals, Clinical Outcome Solutions, Endoceutics, Ixchelsis, Palatin Technologies, Sprout Pharmaceuticals, Strategic Science Technologies, and Valeant. Leonard R. Derogatis has received research support or consulting fees from AMAG Pharmaceuticals and Palatin Technologies. Sally Greenberg has received research support or consulting fees from Palatin Technologies. Anita H. Clayton has received royalties from Ballantine Books/Random House, Changes in Sexual Functioning Questionnaire, and Guilford Publications; has received research support or consulting fees from Alkermes, AMAG Pharmaceuticals, Endoceutics, Fabre-Kramer, Ivix, Janssen, Palatin Technologies, Sage Therapeutics, S1 Biopharma, Sprout, Takeda, and Valeant Pharmaceuticals; and has stocks, stock options, or ownership interest, excluding diversified mutual funds, in Euthymics and S1 Biopharma. Robert Jordan, Johna Lucas, and Carl Spana are employees and stockholders of Palatin Technologies.We thank Linn?a Elliott and Maria Vinall of The Curry Rockefeller Group for editorial assistance (funded by Palatin Technologies). Additional editorial support in the preparation of this manuscript was provided by Phase Five Communications, funded by AMAG Pharmaceuticals, the licensee of bremelanotide. The authors are responsible for all content and editorial decisions, and received no honoraria related to the development of this manuscript. Conflicts of interest: Stanley Althof has received research support or consulting fees from AMAG Pharmaceuticals, Clinical Outcome Solutions, Endoceutics, Ixchelsis, Palatin Technologies, Sprout Pharmaceuticals, Strategic Science Technologies, and Valeant. Leonard R. Derogatis has received research support or consulting fees from AMAG Pharmaceuticals and Palatin Technologies. Sally Greenberg has received research support or consulting fees from Palatin Technologies. Anita H. Clayton has received royalties from Ballantine Books/Random House, Changes in Sexual Functioning Questionnaire, and Guilford Publications; has received research support or consulting fees from Alkermes, AMAG Pharmaceuticals, Endoceutics, Fabre-Kramer, Ivix, Janssen, Palatin Technologies, Sage Therapeutics, S1 Biopharma, Sprout, Takeda, and Valeant Pharmaceuticals; and has stocks, stock options, or ownership interest, excluding diversified mutual funds, in Euthymics and S1 Biopharma. Robert Jordan, Johna Lucas, and Carl Spana are employees and stockholders of Palatin Technologies. Funding: This study was sponsored by Palatin Technologies, the innovator of bremelanotide.
Publisher Copyright:
© 2019 International Society for Sexual Medicine
PY - 2019/8
Y1 - 2019/8
N2 - Background: Responder analyses are used to determine whether changes that occur during a clinical trial are clinically meaningful; for subjective endpoints such as those based on patient-reported outcomes (PROs), responder analyses are particularly useful. Aim: To identify the minimal clinically important difference (MCID) for selected scores on questionnaires assessing female sexual functioning and to use these differences to analyze the response in a large, controlled, phase 2b, dose-finding study of bremelanotide in premenopausal women with hypoactive sexual desire disorder (HSDD) and mixed HSDD/female sexual arousal disorder (FSAD). Methods: The responder analyses were performed for the change from baseline to end of study for a total of 7 endpoints. Each PRO endpoint was assessed using at least 1 of 4 types of responder analyses: a planned analysis anchored to MCIDs based on expert estimates (historical anchors); post hoc analyses based on self-reported global benefit; receiver operating characteristic (ROC) curves; and cumulative distribution function. The prespecified analysis groups were all female sexual dysfunction (FSD)-based diagnoses (all study participants), those with HSDD alone, and a combined group of those with FSAD alone plus those with mixed HSDD/FSAD. Post hoc analyses were also performed for subjects with mixed HSDD/FSAD with a primary diagnosis of HSDD. Outcomes: MCIDs based on the ROC curves for changes in Female Sexual Function Index–desire domain, Female Sexual Distress Scale–Desire/Arousal/Orgasm (FSDS-DAO) total score, FSDS-DAO item 13 and 14 scores, and number of satisfying sexual events. Results: Outcomes matched those based on input from clinical experts. For all 7 endpoints, responder rates at the 1.75 mg dose in the overall modified intention-to-treat population achieved statistical significance compared with placebo (P ≤ .03). Clinical Implications: These responder definitions were subsequently used in the bremelanotide phase 3 registration studies (RECONNECT) that evaluated the safety and efficacy of the bremelanotide 1.75 mg subcutaneous dose in premenopausal women with HSDD. Strengths & Limitations: MCIDs for this study were based on changes from a single-blind phase to account for changes due to the placebo effect. These analyses were restricted to a study population composed only of premenopausal women with a clinical diagnosis of HSDD and/or FSAD and were based on data from the same clinical trial. Conclusion: Bremelanotide was safe and well tolerated and demonstrated significant improvement in efficacy vs placebo in the phase 2b trial. The multiple responder analyses offer a valuable approach for determining clinically important effects of bremelanotide for HSDD and FSAD. Althof S, Derogatis LR, Greenberg S, et al. Responder Analyses from a Phase 2b Dose-Ranging Study of Bremelanotide. J Sex Med 2019;16:1226–1235.
AB - Background: Responder analyses are used to determine whether changes that occur during a clinical trial are clinically meaningful; for subjective endpoints such as those based on patient-reported outcomes (PROs), responder analyses are particularly useful. Aim: To identify the minimal clinically important difference (MCID) for selected scores on questionnaires assessing female sexual functioning and to use these differences to analyze the response in a large, controlled, phase 2b, dose-finding study of bremelanotide in premenopausal women with hypoactive sexual desire disorder (HSDD) and mixed HSDD/female sexual arousal disorder (FSAD). Methods: The responder analyses were performed for the change from baseline to end of study for a total of 7 endpoints. Each PRO endpoint was assessed using at least 1 of 4 types of responder analyses: a planned analysis anchored to MCIDs based on expert estimates (historical anchors); post hoc analyses based on self-reported global benefit; receiver operating characteristic (ROC) curves; and cumulative distribution function. The prespecified analysis groups were all female sexual dysfunction (FSD)-based diagnoses (all study participants), those with HSDD alone, and a combined group of those with FSAD alone plus those with mixed HSDD/FSAD. Post hoc analyses were also performed for subjects with mixed HSDD/FSAD with a primary diagnosis of HSDD. Outcomes: MCIDs based on the ROC curves for changes in Female Sexual Function Index–desire domain, Female Sexual Distress Scale–Desire/Arousal/Orgasm (FSDS-DAO) total score, FSDS-DAO item 13 and 14 scores, and number of satisfying sexual events. Results: Outcomes matched those based on input from clinical experts. For all 7 endpoints, responder rates at the 1.75 mg dose in the overall modified intention-to-treat population achieved statistical significance compared with placebo (P ≤ .03). Clinical Implications: These responder definitions were subsequently used in the bremelanotide phase 3 registration studies (RECONNECT) that evaluated the safety and efficacy of the bremelanotide 1.75 mg subcutaneous dose in premenopausal women with HSDD. Strengths & Limitations: MCIDs for this study were based on changes from a single-blind phase to account for changes due to the placebo effect. These analyses were restricted to a study population composed only of premenopausal women with a clinical diagnosis of HSDD and/or FSAD and were based on data from the same clinical trial. Conclusion: Bremelanotide was safe and well tolerated and demonstrated significant improvement in efficacy vs placebo in the phase 2b trial. The multiple responder analyses offer a valuable approach for determining clinically important effects of bremelanotide for HSDD and FSAD. Althof S, Derogatis LR, Greenberg S, et al. Responder Analyses from a Phase 2b Dose-Ranging Study of Bremelanotide. J Sex Med 2019;16:1226–1235.
KW - Bremelanotide
KW - Female Sexual Dysfunction
KW - Hypoactive Sexual Desire Disorder
KW - Minimal Clinically Important Difference
KW - Responder Analyses
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U2 - 10.1016/j.jsxm.2019.05.012
DO - 10.1016/j.jsxm.2019.05.012
M3 - Article
C2 - 31277966
AN - SCOPUS:85068174112
SN - 1743-6095
VL - 16
SP - 1226
EP - 1235
JO - Journal of Sexual Medicine
JF - Journal of Sexual Medicine
IS - 8
ER -