Drugs

Drug Trials Snapshots: ADDYI

HOW TO USE THIS SNAPSHOT
The information provided in Snapshots highlights who participated in the clinical trials that supported the FDA approval of this drug, and whether there were differences among sex, race, and age groups. The “MORE INFO” bar shows more detailed, technical content for each section. The Snapshot is intended as one tool for consumers to use when discussing the risks and benefits of the drugs.

LIMITATIONS OF THIS SNAPSHOT:
Do not rely on Snapshots to make decisions regarding medical care. Always speak to your health provider about the risks and benefits of a drug. Refer to the ADDYI Prescribing Information for complete information.

ADDYI (flibanserin)
(add-ee)
Sprout Pharmaceuticals, Inc.
Approval date: August 18, 2015


DRUG TRIALS SNAPSHOT SUMMARY:

What is the drug for?

ADDYI is a drug for the treatment of acquired, generalized hypoactive sexual desire disorder (HSDD) in women who have not gone through menopause.

Women with HSDD have low sexual desire that is troubling to them. Their low sexual desire is not due to:

  • a medical or mental health problem
  • problems in the relationship
  • a medicine or other drug use

HSDD is acquired and generalized if the woman has not had problems with low sexual desire in the past, and if she has symptoms no matter the type of sexual activity, the situation, or the sexual partner.

How is this drug used?

ADDYI is a tablet that is taken once daily at bedtime.

What are the benefits of this drug?

In clinical trials, ADDYI increased the number of satisfying sexual events, improved sexual desire and reduced distress related to low sexual desire.  On average, the improvements are small but some women find the improvements to be meaningful.

What are the benefits of this drug (results of trials used to assess efficacy)?

The efficacy of ADDYI was studied in three double-blind, placebo-controlled trials. The efficacy results are based on the full analysis set comprised of all randomized patients who took at least one dose of study medication and had at least one on-treatment efficacy assessment. Missing values were imputed using last-observation-carried-forward. The unadjusted means are presented for the baseline values.

 The table below summarizes the results for the two co-primary efficacy endpoints (satisfying sexual events and sexual desire) and a secondary endpoint (distress related to having low sexual desire) at week 24.

Table 2. Efficacy Results in Premenopausal HSDD Patients by Trial

Full Analysis SetTrial 1Trial 2 1Trial 3
ADDYIPlaceboADDYIPlaceboADDYIPlacebo
n=280n=290n=365n=372n=532n=536
Number of satisfying sexual events (per 28 days)
Baseline (Mean)3.02.72.62.72.52.7
Change from baseline (Mean)1.60.81.81.12.51.5
Treatment diff.0.9 0.6 1.0 
(95% CI)(0.3,1.4) (-0.03, 1.2) (0.4, 1.5) 
Change from baseline (Median)1.0 0.01.0 0.51.0 0.5
Median treatment difference1.0 0.5 0.5 
p-value vs placebop<0.01 p<0.01   p<0.0001 
e-Diary Desire
Baseline (Mean)12.911.812.110.2Not UsedNot Used
Change from baseline at Week 24 (Mean)9.16.98.36.7  
Treatment diff.2.3 1.7   
(95% CI)(-0.1, 4.7) (-0.5, 4.0)   
p-value vs placeboNS NS   
FSFI Desire
Baseline (Mean)1.91.91.81.81.91.9
Change from baseline at Week 24 (Mean)0.90.50.90.51.00.7
Treatment diff.0.4 0.3 0.3 
(95% CI)(0.2, 0.5) (0.2, 0.5) (0.2, 0.4) 
p-value vs placeboN/A 2 N/A 2 p<0.0001 
FSDS-R Question 13 3
Baseline (Mean)3.23.23.23.23.43.4
Change from baseline at Week 24 (Mean)-0.8-0.5-0.8-0.5-1.0-0.7
Treatment diff.-0.4 -0.3 -0.3 
(95% CI)(-0.5, -0.2) (-0.4, -0.1) (-0.4, -0.1) 
p-value vs placeboN/A 2 N/A 2 p=0.0001 

CI = Confidence Interval; NS= not statistically significant; N/A=not applicable
Shaded cells show the results for the co-primary efficacy endpoints for each trial.
e-Diary desire was evaluated as a co-primary endpoint in Trials 1 and 2. FSFI desire was evaluated as a co-primary endpoint in Trial 3 and as a secondary endpoint in Trials 1 and 2.
For satisfying sexual events, p-values are based on the Wilcoxon rank sum test stratified by pooled center. Median change from baseline is shown because the data are not normally distributed.
For FSFI-desire, e-Diary desire, and FSDS-R Question 13, reported p-values are based on an ANCOVA model using baseline as a covariate with treatment and pooled center as main effect terms.  For the change from baseline, the adjusted least squares mean (standard error) are presented.
1Excludes subjects from two study sites that had data integrity issues
2p-value not reported for secondary endpoints because the trial failed on the eDiary Desire co-primary efficacy endpoint
3A decrease in score represents improvement

Source: ADDYI Prescribing Information, Section 14, Table 6

Were there any differences in how well the drug worked in clinical trials among sex, race and age?

Subgroup analysis was conducted for race.

Sex: All patients in the trials were women.

Race: The majority of patients in the trials were white. Differences in how well ADDYI worked among races could not be determined.

Age: All patients in the trials were women between 18 and 56 years of age. Differences in how well ADDYI worked in patients below and above 65 years of age could not be determined.

Were there any differences in how well the drug worked in clinical trials among sex, race, and age groups?

Tables 3, 4, and 5 below summarize the efficacy results by race for the three important outcome measures in clinical trials.

Table 3. Subgroup Analysis by Race: Change From Baseline in Monthly Number of Satisfying Sexual Events (SSEs)*

SubgroupTrial 1
(N=570)
Trial 2
(N=737)
Trial 3
(N=1068)
ADDYI vs. Placebo**95% CIADDYI vs. Placebo**95% CIADDYI vs. Placebo**95% CI
LLULLLULLLUL
Race
White0.90.31.40.5-0.071.10.90.41.5
Black or African American-0.1-2.72.51.2-3.05.40.7-1.32.7
Asian7.6-1.116.40.3-4.45.05.31.49.2
American Indian or Alaska NativeN/AN/AN/AN/AN/AN/A2.9-4.09.8
Native Hawaiian or Other Pacific IslanderN/AN/AN/AN/AN/AN/AN/AN/AN/A

*Full Analysis Population Set
**Treatment difference between ADDYI and placebo was calculated by subtracting the monthly SSEs at baseline from the SSEs at the end of study (Difference >0 indicates treatment benefit of ADDYI compared to Placebo)
LL= lower limit; UL=upper limit; CI = confidence interval; N/A= Not applicable
Source: FDA analysis

Table 4. Subgroup Analysis by Race: Change From Baseline in the Desire Domain of Female Sexual Function Index (FSFI Desire)†*

SubgroupTrial  1
(N=570)
Trial 2
(N=737)
Trial 3
(N=1068)
ADDYI vs. Placebo**95% CIADDYI vs. Placebo95% CIADDYI vs. Placebo95% CI
LLULLLULLLUL
Race 
  White0.30.10.50.40.20.50.40.20.5
  Black or African American0.6-0.041.2-0.2-0.90.6-0.3-0.60.1
  Asian0.7-0.51.90.01-1.41.40.1-2.42.5
  American Indian or Alaska NativeN/AN/AN/AN/AN/AN/A1.60.52.7
  Native Hawaiian or Other Pacific IslanderN/AN/AN/AN/AN/AN/AN/AN/AN/A

* Full Analysis Population Set
** Treatment difference between ADDYI and placebo was calculated by subtracting the monthly FSFI Desire score at baseline from the FSFI Desire score at the end of study (Difference >0 indicates treatment benefit of ADDYI compared to Placebo)
† FSFI desire was evaluated as a secondary endpoint in Trials 1 and 2 and as a co-primary endpoint in Trial 3. e-Diary desire was evaluated as a co-primary endpoint in Trials 1 and 2; Trials 1 and 2 failed on the e-Diary desire so subgroup results are not shown for this endpoint.
LL= lower limit; UL=upper limit; CI = confidence interval; N/A= Not applicable
Source: FDA analysis

Table 5. Subgroup Analysis by Race: Change From Baseline in Distress Measured by Question 13 of the Female Sexual Distress Scale-Revised (FSDS-R Q13)*

SubgroupTrial 1
(N=570)
Trial 2
(N=737)
Trial 3
(N=1068)
ADDYI vs. Placebo**95% CIADDYI vs. Placebo**95% CIADDYI vs. Placebo**95% CI
LLULLLULLLUL
Race 
  White-0.3-0.5-0.1-0.2-0.4-0.1-0.3-0.5-0.2
  Black or African American-0.3-1.00.30.2-0.60.90.2-0.30.6
  Asian-1.8-3.0-0.6-0.7-2.71.4-0.6-1.60.5
  American Indian or Alaska NativeN/AN/AN/AN/AN/AN/A-1.0-3.21.2
  Native Hawaiian or Other Pacific IslanderN/AN/AN/AN/AN/AN/AN/AN/AN/A

* Full Analysis Population Set
** Treatment difference between ADDYI and placebo was calculated by subtracting the monthly FSDS-R Q13 score at baseline from the FSDS-R Q13 score at the end of study (Difference <0 indicates treatment benefit of ADDYI compared to Placebo)
LL= lower limit; UL=upper limit; CI = confidence interval; N/A= Not applicable
Source: FDA analysis

What are the possible side effects?

The most common side effects are dizziness, sleepiness, nausea, fatigue, insomnia, and dry mouth.

ADDYI may cause severe low blood pressure and fainting (loss of consciousness). Patients who use alcohol or who have liver problems must not take ADDYI because they will be at increased risk of severe low blood pressure and fainting (loss of consciousness). Taking ADDYI with certain medications also increases these risks. Patients should discuss all of their medications with their healthcare provider before being prescribed ADDYI. Patients should not start taking new medicines while taking ADDYI until checking it is safe to do so with their healthcare provider.

What are the possible side effects (results of trials used to assess safety)?

The table below summarizes adverse reactions for the pooled four trials. The population represented is the Safety population, which includes any patient who received at least one dose of ADDYI or placebo drug.

Table 5. Adverse Reactions Reported in ≥2% of Patients Receiving ADDYI and at a Higher Incidence than Placebo-treated Patients

Adverse ReactionPlacebo
(N=1556)
ADDYI
(N=1543)
Dizziness2.2%11.4%
Somnolence2.9%11.2%
Nausea3.9%10.4%
Fatigue5.5%9.2%
Insomnia2.8%4.9%
Dry mouth1%2.4%

Source: ADDYI Prescribing Information, Section 6, Table 2

Were there any differences in side effects among sex, race and age?

Subgroup analysis was conducted for race.

Sex: All patients in the trials were women.

Race: The majority of patients in the trials were white. Differences in side effects among races could not be determined.

Age: All patients in the trials were women between 18 and 56 years of age. Differences in side effects in patients below and above 65 years of age could not be determined.

Were there any differences in side effects of the clinical trials among sex, race, and age groups?

The tables below summarize dizziness, somnolence, and nausea by race. The population represented is the Safety population, which includes any patient who received at least one dose of ADDYI or placebo drug.

Table 6.  Subgroup Analysis of Adverse Event-Dizziness

SubgroupADDYI
(N=1543)
Placebo
(N=1556)
n (%)Total, nn (%)Total, n
White163 (12.0)136434 (2.5)1379
Black or African American6 (4.5)1340 (0.0)122
Asian3 (14.3)210 (0.0)21
American Indian or Alaska Native1 (50.0)20 (0.0)7
Native Hawaiian or Other Pacific Islander0 (0.0)10 (0.0)2
Unknown3 (14.3)210 (0.0)25

Source: Company Trial Data

Table 7. Subgroup Analysis of Adverse Event-Somnolence

SubgroupADDYI
 (N=1543)
Placebo
(N=1556)
n (%)Total, nn (%)Total, n
White148 (10.9)136440 (2.9)1379
Black or African American23 (17.2)1342 (1.6)122
Asian2 (9.5)211 (4.8)21
American Indian or Alaska Native0 (0.0)217
Native Hawaiian or Other Pacific Islander0 (0.0)102
Missing0 (0.0)211 (4.0)25

Source: Company Trial Data

Table 8. Subgroup Analysis of Adverse Event-Nausea

SubgroupADDYI
(N=1543)
Placebo
(N=1556)
n (%)Total, nn (%)Total, n
White142 (10.4)136456 (4.1)1379
Black or African American8 (6.0)1344 (3.3)122
Asian6 (2.9)210 (0.0)21
American Indian or Alaska Native1 (50.0)20 (0.0)7
Native Hawaiian or Other Pacific Islander0 (0.0)10 (0.0)2
Unknown4 (19.0)210 (0.0)25

Source: Company Trial Data

WHO WAS IN THE CLINICAL TRIALS?

Who participated in the clinical trials?

The FDA approved ADDYI based on evidence from 4 clinical trials of 3099 women with low sexual desire disorder. The trials were conducted in the United States, Canada, and Europe.

The figure below summarizes how many patients participated by sex in the clinical trials.

Figure 1. Baseline Demographics by Sex

Pie chart summarizing how many men and women were enrolled in the clinical trials used to evaluate efficacy of the drug ADDYI.  In total, 3099 women (100%) participated in the clinical trials used to evaluate efficacy of the drug ADDYI.

Source: Company Trial Data

The figure and table below summarize the percentage of patients by race in the clinical trials.

Figure 2. Baseline Demographics by Race

Pie chart summarizing the percentage of patients by race enrolled in the ADDYI clinical trial. In total, 2743 White (89%), 256 Black (8%), 42 Asian (1%), 9 American Indian or Alaska Native (<1%), 3 Native Hawaiian or Other Pacific Islander (<1%), and 46 identified as Other (2%).

<1%=less than 1%
Source: Company Trial Data

Table 1. Demographics by Race

RaceNumber of PatientsPercentage of Patients
  White274389%
  Black or African American2568%
  Asian421%
  American Indian or Alaska Native9less than 1%
  Native Hawaiian or Other Pacific Islander3less than 1%
Unknown462%

Source: Company Trial Data

The figure below summarizes how many patients by age participated in the clinical trial.

Figure 3. Baseline Demographics by Age

Pie chart summarizing how many individuals of certain age groups were enrolled in the ADDYI clinical trial.  In total, 3099 were between 18 and 56 years (100%).

Source: Company Trial Data

The table below summarizes baseline demographics for the trials (safety population).    

Table 9. Baseline Demographics

 ADDYI
(N=1543)
Placebo
(N=1556)
Total (N=3099)
Sex
 Men0 (0)0 (0)0 (0)
 Women1543 (100%)1556 (100%)  3099 (100%)
Age 
  Mean years (SD)36 (7)36 (7)36 (7)
  Median (years)363636
  Min, Max (years)19, 5618, 5418, 56
Race 
  White1364 (88%)1379 (89%)2743 (89%)
  Black or African American134 (9%)122 (8%)256 (8%)
  Asian21 (1%)21 (1%)42 (1%)
  American Indian or Alaska Native2 (<1%)7 (<1%)9 (<1%)
  Native Hawaiian or Other Pacific Islander1 (<1%)2 (<1%)3 (<1%)
Unknown21 (1%)25 (2%)46 (2%)
Ethnicity 
  Hispanic or Latino126 (8%)114 (7%)240 (8%)
  Not Hispanic or Latino1394 (90%)1416 (91%)2810 (90%)
  Unknown23 (2%)26 (2%)49 (2%)
Region  
  United States1115 (72%)1126 (72%)2241 (72%)
  Canada112 (7%)112 (7%)224 (7%)
  Europe316 (21%)318 (20%)634 (21%)

Source: Company Trial Data

How were the trials designed?

There were four trials that compared the side effects of ADDYI to a placebo. Three of these trials also compared the benefits of ADDYI to a placebo. In each trial, patients received ADDYI or a placebo tablet at bedtime for 24 weeks. Neither the patients nor the health care providers knew which treatment was being given until after the trials were completed.

The trials measured the number of satisfying sexual events, the level of sexual desire and the level of distress related to low sexual desire.

How were the trials designed?

The efficacy of ADDYI for the treatment of HSDD in premenopausal women was evaluated in three 24-week, randomized, double-blind, placebo-controlled trials. The trials included premenopausal women with acquired, generalized HSDD of at least 6 months duration. The patients were treated with either ADDYI 100 mg or placebo once daily at bedtime.

These trials each had two co-primary efficacy endpoints, one for satisfying sexual events and the other for sexual desire. These trials also had a secondary endpoint that evaluated distress related to low sexual desire.

GLOSSARY

CLINICAL TRIAL: Voluntary research studies conducted in people and designed to answer specific questions about the safety or effectiveness of drugs, vaccines, other therapies, or new ways of using existing treatments.
COMPARATOR: A previously available treatment or placebo used in clinical trials that is compared to the actual drug being tested.
EFFICACY: How well the drug achieves the desired response when it is taken as described in a controlled clinical setting, such as during a clinical trial.
PLACEBO: An inactive substance or “sugar pill” that looks the same as, and is given the same way as, an active drug or treatment being tested. The effects of the active drug or treatment are compared to the effects of the placebo.
SUBGROUP: A subset of the population studied in a clinical trial. Demographic subsets include sex, race, and age groups.

PRESCRIBING INFORMATION

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