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 Set | Trial 1 | Trial 2 1 | Trial 3 | |||||
|---|---|---|---|---|---|---|---|---|
| ADDYI | Placebo | ADDYI | Placebo | ADDYI | Placebo | |||
| n=280 | n=290 | n=365 | n=372 | n=532 | n=536 | |||
| Number of satisfying sexual events (per 28 days) | ||||||||
| Baseline (Mean) | 3.0 | 2.7 | 2.6 | 2.7 | 2.5 | 2.7 | ||
| Change from baseline (Mean) | 1.6 | 0.8 | 1.8 | 1.1 | 2.5 | 1.5 | ||
| 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 | 0.0 | 1.0 | 0.5 | 1.0 | 0.5 | ||
| Median treatment difference | 1.0 | 0.5 | 0.5 | |||||
| p-value vs placebo | p<> | p<> | p<> | |||||
| e-Diary Desire | ||||||||
| Baseline (Mean) | 12.9 | 11.8 | 12.1 | 10.2 | Not Used | Not Used | ||
| Change from baseline at Week 24 (Mean) | 9.1 | 6.9 | 8.3 | 6.7 | ||||
| Treatment diff. | 2.3 | 1.7 | ||||||
| (95% CI) | (-0.1, 4.7) | (-0.5, 4.0) | ||||||
| p-value vs placebo | NS | NS | ||||||
| FSFI Desire | ||||||||
| Baseline (Mean) | 1.9 | 1.9 | 1.8 | 1.8 | 1.9 | 1.9 | ||
| Change from baseline at Week 24 (Mean) | 0.9 | 0.5 | 0.9 | 0.5 | 1.0 | 0.7 | ||
| 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 placebo | N/A 2 | N/A 2 | p<> | |||||
| FSDS-R Question 13 3 | ||||||||
| Baseline (Mean) | 3.2 | 3.2 | 3.2 | 3.2 | 3.4 | 3.4 | ||
| 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 placebo | N/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)*
| Subgroup | Trial 1 (N=570) |
Trial 2 (N=737) |
Trial 3 (N=1068) |
||||||
|---|---|---|---|---|---|---|---|---|---|
| ADDYI vs. Placebo** | 95% CI | ADDYI vs. Placebo** | 95% CI | ADDYI vs. Placebo** | 95% CI | ||||
| LL | UL | LL | UL | LL | UL | ||||
| Race | |||||||||
| White | 0.9 | 0.3 | 1.4 | 0.5 | -0.07 | 1.1 | 0.9 | 0.4 | 1.5 |
| Black or African American | -0.1 | -2.7 | 2.5 | 1.2 | -3.0 | 5.4 | 0.7 | -1.3 | 2.7 |
| Asian | 7.6 | -1.1 | 16.4 | 0.3 | -4.4 | 5.0 | 5.3 | 1.4 | 9.2 |
| American Indian or Alaska Native | N/A | N/A | N/A | N/A | N/A | N/A | 2.9 | -4.0 | 9.8 |
| Native Hawaiian or Other Pacific Islander | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/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)†*
| Subgroup | Trial 1 (N=570) |
Trial 2 (N=737) |
Trial 3 (N=1068) |
||||||
|---|---|---|---|---|---|---|---|---|---|
| ADDYI vs. Placebo** | 95% CI | ADDYI vs. Placebo | 95% CI | ADDYI vs. Placebo | 95% CI | ||||
| LL | UL | LL | UL | LL | UL | ||||
| Race | |||||||||
| White | 0.3 | 0.1 | 0.5 | 0.4 | 0.2 | 0.5 | 0.4 | 0.2 | 0.5 |
| Black or African American | 0.6 | -0.04 | 1.2 | -0.2 | -0.9 | 0.6 | -0.3 | -0.6 | 0.1 |
| Asian | 0.7 | -0.5 | 1.9 | 0.01 | -1.4 | 1.4 | 0.1 | -2.4 | 2.5 |
| American Indian or Alaska Native | N/A | N/A | N/A | N/A | N/A | N/A | 1.6 | 0.5 | 2.7 |
| Native Hawaiian or Other Pacific Islander | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/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)*
| Subgroup | Trial 1 (N=570) |
Trial 2 (N=737) |
Trial 3 (N=1068) |
||||||
|---|---|---|---|---|---|---|---|---|---|
| ADDYI vs. Placebo** | 95% CI | ADDYI vs. Placebo** | 95% CI | ADDYI vs. Placebo** | 95% CI | ||||
| LL | UL | LL | UL | LL | UL | ||||
| 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 | -1.0 | 0.3 | 0.2 | -0.6 | 0.9 | 0.2 | -0.3 | 0.6 |
| Asian | -1.8 | -3.0 | -0.6 | -0.7 | -2.7 | 1.4 | -0.6 | -1.6 | 0.5 |
| American Indian or Alaska Native | N/A | N/A | N/A | N/A | N/A | N/A | -1.0 | -3.2 | 1.2 |
| Native Hawaiian or Other Pacific Islander | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/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="">
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 Reaction | Placebo (N=1556) |
ADDYI (N=1543) |
|---|---|---|
| Dizziness | 2.2% | 11.4% |
| Somnolence | 2.9% | 11.2% |
| Nausea | 3.9% | 10.4% |
| Fatigue | 5.5% | 9.2% |
| Insomnia | 2.8% | 4.9% |
| Dry mouth | 1% | 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
| Subgroup | ADDYI (N=1543) |
Placebo (N=1556) |
||
|---|---|---|---|---|
| n (%) | Total, n | n (%) | Total, n | |
| White | 163 (12.0) | 1364 | 34 (2.5) | 1379 |
| Black or African American | 6 (4.5) | 134 | 0 (0.0) | 122 |
| Asian | 3 (14.3) | 21 | 0 (0.0) | 21 |
| American Indian or Alaska Native | 1 (50.0) | 2 | 0 (0.0) | 7 |
| Native Hawaiian or Other Pacific Islander | 0 (0.0) | 1 | 0 (0.0) | 2 |
| Unknown | 3 (14.3) | 21 | 0 (0.0) | 25 |
Source: Company Trial Data
Table 7. Subgroup Analysis of Adverse Event-Somnolence
| Subgroup | ADDYI (N=1543) |
Placebo (N=1556) |
||
|---|---|---|---|---|
| n (%) | Total, n | n (%) | Total, n | |
| White | 148 (10.9) | 1364 | 40 (2.9) | 1379 |
| Black or African American | 23 (17.2) | 134 | 2 (1.6) | 122 |
| Asian | 2 (9.5) | 21 | 1 (4.8) | 21 |
| American Indian or Alaska Native | 0 (0.0) | 2 | 1 | 7 |
| Native Hawaiian or Other Pacific Islander | 0 (0.0) | 1 | 0 | 2 |
| Missing | 0 (0.0) | 21 | 1 (4.0) | 25 |
Source: Company Trial Data
Table 8. Subgroup Analysis of Adverse Event-Nausea
| Subgroup | ADDYI (N=1543) |
Placebo (N=1556) |
||
|---|---|---|---|---|
| n (%) | Total, n | n (%) | Total, n | |
| White | 142 (10.4) | 1364 | 56 (4.1) | 1379 |
| Black or African American | 8 (6.0) | 134 | 4 (3.3) | 122 |
| Asian | 6 (2.9) | 21 | 0 (0.0) | 21 |
| American Indian or Alaska Native | 1 (50.0) | 2 | 0 (0.0) | 7 |
| Native Hawaiian or Other Pacific Islander | 0 (0.0) | 1 | 0 (0.0) | 2 |
| Unknown | 4 (19.0) | 21 | 0 (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
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
<1%=less than="">
Source: Company Trial Data
Table 1. Demographics by Race
| Race | Number of Patients | Percentage of Patients |
|---|---|---|
| White | 2743 | 89% |
| Black or African American | 256 | 8% |
| Asian | 42 | 1% |
| American Indian or Alaska Native | 9 | less than 1% |
| Native Hawaiian or Other Pacific Islander | 3 | less than 1% |
| Unknown | 46 | 2% |
Source: Company Trial Data
The figure below summarizes how many patients by age participated in the clinical trial.
Figure 3. Baseline Demographics by Age
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 | |||
| Men | 0 (0) | 0 (0) | 0 (0) |
| Women | 1543 (100%) | 1556 (100%) | 3099 (100%) |
| Age | |||
| Mean years (SD) | 36 (7) | 36 (7) | 36 (7) |
| Median (years) | 36 | 36 | 36 |
| Min, Max (years) | 19, 56 | 18, 54 | 18, 56 |
| Race | |||
| White | 1364 (88%) | 1379 (89%) | 2743 (89%) |
| Black or African American | 134 (9%) | 122 (8%) | 256 (8%) |
| Asian | 21 (1%) | 21 (1%) | 42 (1%) |
| American Indian or Alaska Native | 2 (<1%) | 7 (<1%) | 9 (<1%) |
| Native Hawaiian or Other Pacific Islander | 1 (<1%) | 2 (<1%) | 3 (<1%) |
| Unknown | 21 (1%) | 25 (2%) | 46 (2%) |
| Ethnicity | |||
| Hispanic or Latino | 126 (8%) | 114 (7%) | 240 (8%) |
| Not Hispanic or Latino | 1394 (90%) | 1416 (91%) | 2810 (90%) |
| Unknown | 23 (2%) | 26 (2%) | 49 (2%) |
| Region | |||
| United States | 1115 (72%) | 1126 (72%) | 2241 (72%) |
| Canada | 112 (7%) | 112 (7%) | 224 (7%) |
| Europe | 316 (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.