Endometriosis-related Pain
Conditions
Brief summary
The purpose of this study is to evaluate the efficacy, safety, and tolerability of gefapixant (MK-7264) in premenopausal female participants with moderate to severe endometriosis-related pain. The primary hypothesis: gefapixant is superior to placebo in reducing the average daily pelvic pain score (cyclic and non-cyclic, combined) during Treatment Cycle 2.
Interventions
DRUGGefapixant
Gefapixant tablet 45 mg taken orally
DRUGPlacebo
Placebo matching gefapixant tablet taken orally
DRUGNaproxen
Naproxen sodium 275 mg tablets taken orally as needed, at dose prescribed by sites' principal investigator
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 49 Years
Healthy volunteers
No
Inclusion criteria
* has been surgically (laparoscopy or laparotomy) diagnosed with endometriosis. * has cyclic AND non-cyclic, moderate to severe endometriosis-related pelvic pain (overall pelvic pain score ≥5 using a 0-10 NRS, with 0 representing no pain and 10 representing extremely severe pain). * has had spontaneous menstrual cycles before Visit 1. * has body mass index (BMI) between 18 kg/m\^2 to 40 kg/m\^2 at Visit 1. * is not pregnant, not breastfeeding, and agrees to follow the contraceptive guidance. * must agree to switch from her usual analgesic medication to only that which is permitted in the study.
Exclusion criteria
* history of hysterectomy and/or bilateral oophorectomy. * has undiagnosed vaginal bleeding. * has chronic, non-pelvic pain not caused by endometriosis that requires chronic analgesic. * has a clinically significant gynecologic condition identified in the screening evaluation. * has a history of anaphylaxis or cutaneous adverse drug reaction (with or without systemic symptoms) to sulfonamide antibiotics or other sulfonamide-containing drugs. * has a known allergy/sensitivity or contraindication to gefapixant or its excipients. * has an allergy/sensitivity/intolerance to naproxen sodium (rescue medication) or any contraindication to its use, or has experienced asthma, urticaria, or allergic-type reactions after taking aspirin or other nonsteroidal anti-inflammatory drugs (NSAIDs). * has a history of endometriosis-related pain that was non-responsive to treatment with combined hormonal contraceptives (CHCs), gonadotropin-releasing hormone (GnRH) antagonists, GnRH agonists, progestins, or aromatase inhibitors. * has a positive urine pregnancy test at any time before randomization. * has required more than 2 weeks of continuous use of narcotics for treatment of endometriosis-related pain within 6 months of Visit 1.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Average Daily Pelvic Pain Score During Treatment Cycle 2 | Baseline and Treatment Cycle 2 (Week 4 to Week 8; each cycle is approximately 28 days) | Pelvic pain (cyclic pain associated with menses, and non-cyclic pain not associated with menses) severity score was measured using a 0-10 numeric rating scale (NRS), with 0 representing no pain and 10 representing extremely severe pain. The averages of the daily pelvic pain scores (cyclic and non-cyclic, combined) entered in participants' electronic diaries (eDiaries) were calculated for Baseline and Treatment Cycle 2 (approximately Week 4 to Week 8). A negative change indicates a decrease in pain severity from baseline. |
| Percentage of Participants Who Experienced an Adverse Event | Up to approximately 10 weeks | An adverse event (AE) is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. Per protocol, this analysis included AEs reported up to 14 days after end of study intervention. |
| Percentage of Participants Who Discontinued Study Drug Due to an Adverse Event | Up to approximately 8 weeks | An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Average Daily Cyclic Pelvic Pain Score During Treatment Cycle 2 | Baseline and Treatment Cycle 2 (Week 4 to Week 8; each cycle is approximately 28 days) | Cyclic pelvic pain (associated with menses) severity score was measured using a 0-10 NRS, with 0 representing no pain and 10 representing extremely severe pain. The average of the daily cyclic pelvic pain scores entered in participants' eDiaries was calculated for Baseline and Treatment Cycle 2 (Week 4 to Week 8). A negative change indicates a decrease in pain severity from baseline. |
| Change From Baseline in Average Daily Non-Cyclic Pelvic Pain Score During Treatment Cycle 2 | Baseline and Treatment Cycle 2 (Week 4 to Week 8; each cycle is approximately 28 days) | Non-cyclic pelvic pain (not associated with menses) severity score was measured using a 0-10 NRS, with 0 representing no pain and 10 representing extremely severe pain. The average of the non-cyclic daily pelvic pain scores entered in participants' eDiaries was calculated for the Baseline and Treatment Cycle 2 (Week 4 to Week 8). A negative change indicates decrease in pain severity from baseline. |
Countries
Australia, Chile, New Zealand, Poland, Puerto Rico, Russia, Spain, Ukraine, United States
Participant flow
Pre-assignment details
This study included a baseline menstrual cycle (approximately 4 weeks) prior to randomization to either gefapixant or placebo.
Participants by arm
| Arm | Count |
|---|---|
| Gefapixant Participants received a gefapixant 45 mg tablet twice a day for approximately 8 weeks (2 menstrual cycles). Naproxen sodium 275 mg tablets were also provided to participants, as needed, for endometriosis-related pain. | 94 |
| Placebo Participants received a placebo matching gefapixant tablet twice a day for approximately 8 weeks (2 menstrual cycles). Naproxen sodium 275 mg tablets were also provided to participants, as needed, for endometriosis-related pain. | 93 |
| Total | 187 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 1 | 1 |
| Overall Study | Physician Decision | 0 | 1 |
| Overall Study | Unable to adhere to study schedule | 0 | 1 |
| Overall Study | Withdrawal by Subject | 5 | 3 |
Baseline characteristics
| Characteristic | Gefapixant | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 34.5 Years STANDARD_DEVIATION 6.6 | 34.8 Years STANDARD_DEVIATION 7.3 | 34.6 Years STANDARD_DEVIATION 6.9 |
| Average Daily Pelvic Pain Score | 6.5 Scores on a scale STANDARD_DEVIATION 1 | 6.5 Scores on a scale STANDARD_DEVIATION 1 | 6.5 Scores on a scale STANDARD_DEVIATION 1 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 35 Participants | 31 Participants | 66 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 59 Participants | 62 Participants | 121 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 4 Participants | 3 Participants | 7 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 4 Participants | 5 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 88 Participants | 86 Participants | 174 Participants |
| Sex: Female, Male Female | 94 Participants | 93 Participants | 187 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 94 | 0 / 93 |
| other Total, other adverse events | 36 / 94 | 12 / 93 |
| serious Total, serious adverse events | 0 / 94 | 0 / 93 |
Outcome results
Primary
Change From Baseline in Average Daily Pelvic Pain Score During Treatment Cycle 2
Pelvic pain (cyclic pain associated with menses, and non-cyclic pain not associated with menses) severity score was measured using a 0-10 numeric rating scale (NRS), with 0 representing no pain and 10 representing extremely severe pain. The averages of the daily pelvic pain scores (cyclic and non-cyclic, combined) entered in participants' electronic diaries (eDiaries) were calculated for Baseline and Treatment Cycle 2 (approximately Week 4 to Week 8). A negative change indicates a decrease in pain severity from baseline.
Time frame: Baseline and Treatment Cycle 2 (Week 4 to Week 8; each cycle is approximately 28 days)
Population: All randomized participants who received at least one dose of double-blind study intervention and had at least one day of eDiary entries during the post-randomization treatment cycle.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Gefapixant | Change From Baseline in Average Daily Pelvic Pain Score During Treatment Cycle 2 | -2.2 Scores on a Scale |
| Placebo | Change From Baseline in Average Daily Pelvic Pain Score During Treatment Cycle 2 | -1.7 Scores on a Scale |
p-value: 0.06695% CI: [-1.01, 0.03]ANCOVA
Primary
Percentage of Participants Who Discontinued Study Drug Due to an Adverse Event
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention.
Time frame: Up to approximately 8 weeks
Population: All randomized participants who received at least one dose of study intervention.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Gefapixant | Percentage of Participants Who Discontinued Study Drug Due to an Adverse Event | 3.2 Percentage of Participants |
| Placebo | Percentage of Participants Who Discontinued Study Drug Due to an Adverse Event | 0.0 Percentage of Participants |
95% CI: [-0.9, 9]
Primary
Percentage of Participants Who Experienced an Adverse Event
An adverse event (AE) is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. Per protocol, this analysis included AEs reported up to 14 days after end of study intervention.
Time frame: Up to approximately 10 weeks
Population: All randomized participants who received at least one dose of study intervention.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Gefapixant | Percentage of Participants Who Experienced an Adverse Event | 53.2 Percentage of Participants |
| Placebo | Percentage of Participants Who Experienced an Adverse Event | 35.5 Percentage of Participants |
95% CI: [3.4, 31.3]
Secondary
Change From Baseline in Average Daily Cyclic Pelvic Pain Score During Treatment Cycle 2
Cyclic pelvic pain (associated with menses) severity score was measured using a 0-10 NRS, with 0 representing no pain and 10 representing extremely severe pain. The average of the daily cyclic pelvic pain scores entered in participants' eDiaries was calculated for Baseline and Treatment Cycle 2 (Week 4 to Week 8). A negative change indicates a decrease in pain severity from baseline.
Time frame: Baseline and Treatment Cycle 2 (Week 4 to Week 8; each cycle is approximately 28 days)
Population: All randomized participants who received at least one dose of double-blind study intervention, had at least one day of eDiary entry during the post-randomization treatment cycle, and had available cyclic pelvic pain score data.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Gefapixant | Change From Baseline in Average Daily Cyclic Pelvic Pain Score During Treatment Cycle 2 | -2.0 Scores on a Scale |
| Placebo | Change From Baseline in Average Daily Cyclic Pelvic Pain Score During Treatment Cycle 2 | -1.3 Scores on a Scale |
95% CI: [-1.18, -0.06]
Secondary
Change From Baseline in Average Daily Non-Cyclic Pelvic Pain Score During Treatment Cycle 2
Non-cyclic pelvic pain (not associated with menses) severity score was measured using a 0-10 NRS, with 0 representing no pain and 10 representing extremely severe pain. The average of the non-cyclic daily pelvic pain scores entered in participants' eDiaries was calculated for the Baseline and Treatment Cycle 2 (Week 4 to Week 8). A negative change indicates decrease in pain severity from baseline.
Time frame: Baseline and Treatment Cycle 2 (Week 4 to Week 8; each cycle is approximately 28 days)
Population: All randomized participants who received at least one dose of double-blind study intervention, had at least one day of eDiary entry during the post-randomization treatment cycle, and had available non-cyclic pelvic pain score data.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Gefapixant | Change From Baseline in Average Daily Non-Cyclic Pelvic Pain Score During Treatment Cycle 2 | -2.3 Scores on a Scale |
| Placebo | Change From Baseline in Average Daily Non-Cyclic Pelvic Pain Score During Treatment Cycle 2 | -1.8 Scores on a Scale |
95% CI: [-1.04, 0.03]