A Study to Evaluate the Efficacy and Safety of Gefapixant (MK-7264) in Women With Endometriosis-Related Pain (MK-7264-034)

• Sponsor: Merck Sharp & Dohme LLC (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03654326
• Collaborator: (none)
• Enrollment: 187
• Locations: 78
• Arms: 2
• Actual Duration (Months): 21.6
• Patients Per Site: 2.4
• Patients Per Site Per Month: 0.1

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Endometriosis-related Pain	Drug: Gefapixant; Drug: Placebo; Drug: Naproxen	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 187 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: A Phase 2a, Proof of Concept, Randomized, Double-Blind, Placebo-Controlled Clinical Trial, to Evaluate the Efficacy and Safety of MK-7264 in Women With Moderate to Severe Endometriosis-Related Pain
• Actual Study Start Date: Sep 11, 2018
• Actual Primary Completion Date: Jun 30, 2020
• Actual Study Completion Date: Jun 30, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Gefapixant Participants will receive a gefapixant 45 mg tablet twice a day for approximately 8 weeks (2 menstrual cycles). Naproxen sodium 275 mg tablets will also be provided to participants for use as rescue medication for endometriosis-related pain.	Drug: Gefapixant; Gefapixant tablet 45 mg taken orally; Other Names: MK-7264 ; Drug: Placebo; Placebo matching gefapixant tablet taken orally; Drug: Naproxen; Naproxen sodium 275 mg tablets taken orally as needed, at dose prescribed by sites' principal investigator
Placebo Comparator: Placebo Participants will receive a placebo matching gefapixant tablet twice a day for approximately 8 weeks (2 menstrual cycles). Naproxen sodium 275 mg tablets will also be provided to participants for use as rescue medication for endometriosis-related pain.	Drug: Placebo; Placebo matching gefapixant tablet taken orally; Drug: Naproxen; Naproxen sodium 275 mg tablets taken orally as needed, at dose prescribed by sites' principal investigator

Outcome Measures

Primary Outcome Measures

1. 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.

2. 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.

3. 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 Outcome Measures

1. 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.

2. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 49 Years
• Sexes Eligible for Study: Female
• Accepts 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Cahaba Medical Care ( Site 0750)	Birmingham	Alabama	United States	35218
2	Synexus US Phoenix Southeast ( Site 0729)	Chandler	Arizona	United States	85224
3	Synexus ( Site 0734)	Scottsdale	Arizona	United States	85251
4	Lynn Institute of the Ozarks ( Site 0720)	Little Rock	Arkansas	United States	72205
5	California Center for Clinical Research ( Site 0741)	Arcadia	California	United States	91007
6	Artemis Institute for Clinical Research ( Site 0716)	San Diego	California	United States	92103
7	Alta California Medical Group ( Site 0721)	Simi Valley	California	United States	93065
8	Thameside OBGYN Center ( Site 0747)	Groton	Connecticut	United States	06340
9	WHUSA Fine and Gillette ( Site 0751)	Hamden	Connecticut	United States	06518
10	Florida Fertility Institute ( Site 0737)	Clearwater	Florida	United States	33759
11	Advanced Pharma Research ( Site 0719)	Cutler Bay	Florida	United States	33189
12	Doral Medical Research, LLC ( Site 0706)	Doral	Florida	United States	33166
13	KO Clinical Research, LLC ( Site 0723)	Fort Lauderdale	Florida	United States	33316
14	Inpatient Research Clinic, LLC ( Site 0725)	Miami Lakes	Florida	United States	33014
15	Well Pharma Medical Research, Corp. ( Site 0703)	Miami	Florida	United States	33143
16	L&C Professional Medical Research Institute ( Site 0709)	Miami	Florida	United States	33144
17	New Horizon Research Center ( Site 0717)	Miami	Florida	United States	33465
18	QPS Miami Research Associates ( Site 0735)	South Miami	Florida	United States	33143
19	Lenus Research & Medical Group Llc ( Site 0702)	Sweetwater	Florida	United States	33172
20	Southern Clinical Research Associates ( Site 0701)	Metairie	Louisiana	United States	70001
21	Tufts Medical Center ( Site 0742)	Boston	Massachusetts	United States	02111
22	Carolina Women's Research and Wellness Center ( Site 0715)	Durham	North Carolina	United States	27713
23	Palmetto Clinical Research ( Site 0707)	Summerville	South Carolina	United States	29485
24	Chattanooga Medical Research ( Site 0743)	Chattanooga	Tennessee	United States	37404
25	Women Partners in Health ( Site 0745)	Austin	Texas	United States	78705
26	Corpus Christi Clinic ( Site 0744)	Corpus Christi	Texas	United States	78412
27	HD Research Corp ( Site 0738)	Houston	Texas	United States	77024
28	PI-Coor Clinical Research, LLC ( Site 0710)	Reston	Virginia	United States	20190
29	Clinical Research Partners, LLC. ( Site 0704)	Richmond	Virginia	United States	23225
30	Seattle Women's: Health, Research, Gynecology ( Site 0714)	Seattle	Washington	United States	98105
31	Paratus Clinical Kanwal ( Site 0004)	Kanwal	New South Wales	Australia	2259
32	Royal Hospital for Women ( Site 0008)	Randwick	New South Wales	Australia	2031
33	Holdsworth House Medical Practice ( Site 0009)	Sydney	New South Wales	Australia	2010
34	Royal Adelaide Hospital ( Site 0007)	Adelaide	South Australia	Australia	5000
35	Keogh Institute for Medical Research ( Site 0002)	Nedlands	Western Australia	Australia	6009
36	Hospital San Juan de Dios de La Serena ( Site 0110)	La Serena	Region De Coquimbo	Chile	1710216
37	Hospital San Borja Arriaran ( Site 0103)	Santiago	Region Metropolitana	Chile	8360160
38	Clinica Indisa [Santiago, Chile] ( Site 0101)	Santiago		Chile	7520440
39	Clinica Las Condes ( Site 0109)	Santiago		Chile	7591047
40	Clinica Alemana de Santiago ( Site 0107)	Santiago		Chile	7650568
41	Southern Clinical Trials - Waitemata ( Site 0200)	Auckland		New Zealand	0626
42	Southern Clinical Trials Ltd ( Site 0201)	Christchurch		New Zealand	8013
43	Prywatna Klinika Polozniczo - Ginekologiczna ( Site 0300)	Bialystok		Poland	15-224
44	Indywidualna Specjalistyczna Praktyka Lekarska Krzysztof Wilk ( Site 0316)	Katowice		Poland	40-301
45	SPL Chorob Kobiecych i Połoznictwa dr L. Kobielska ( Site 0339)	Katowice		Poland	40-717
46	Clinical Medical Research Sp. z o.o. ( Site 0343)	Katowice		Poland	40-750
47	Osrodek Badan Klinicznych Gyncentrum ( Site 0330)	Katowice		Poland	40-851
48	LIFTMED ( Site 0325)	Rybnik		Poland	44-200
49	Examen Sp. z o.o. ( Site 0318)	Skorzewo		Poland	60-185
50	Clinical Best Solutions ( Site 0338)	Warszawa		Poland	02-793
51	Marek Elias Gabinety Ginekologiczne ( Site 0331)	Wroclaw		Poland	50-547
52	Cooperativa de Facultad Medica Sanacoop ( Site 0805)	Bayamon		Puerto Rico	00961
53	Ponce Health Sciences University ( Site 0804)	Ponce		Puerto Rico	00717-2348
54	Gynecology & Endometriosis Center LLC ( Site 0806)	San Juan		Puerto Rico	00909
55	Henry A. Rodriguez-Ginorio Private Practice ( Site 0800)	San Juan		Puerto Rico	00917
56	Genes Fertility Institute Inc. ( Site 0803)	San Juan		Puerto Rico	00918
57	Kazan State Medical University ( Site 0404)	Kazan		Russian Federation	420029
58	Clinical Hospital #2 of Kazan city ( Site 0406)	Kazan		Russian Federation	420033
59	LLC Scientific Research Medical Complex Your Health. ( Site 0405)	Kazan		Russian Federation	420097
60	Moscow Regional Research Institute of Tocology and Gynecolog ( Site 0411)	Moscow		Russian Federation	101000
61	State Institution of Healthcare Moscow City Clinical Hospital 13 ( Site 0408)	Moscow		Russian Federation	115280
62	NII of Obstetrics, Gynecology and Reproductology n.a. D.O. Ott ( Site 0401)	Saint Petersburg		Russian Federation	199034
63	Uromed LLC ( Site 0410)	Smolensk		Russian Federation	214031
64	Women clinic 22 ( Site 0400)	St. Petersburg		Russian Federation	194354
65	Siberian State Medical University ( Site 0402)	Tomsk		Russian Federation	634050
66	Hospital Sanitas La Zarzuela ( Site 0502)	Aravaca	Madrid	Spain	28023
67	Instituto de Ciencias Medicas.ICM ( Site 0500)	Alicante		Spain	03004
68	Hospital Clinic i Provincial de Barcelona ( Site 0501)	Barcelona		Spain	08036
69	Hospital Sanitas La Moraleja ( Site 0504)	Madrid		Spain	28050
70	Iv-Fr Reg Perinatal center State higher Educa inst Iv-Fr Nat Med University ( Site 0910)	Ivano-Frankivsk		Ukraine	76018
71	Medical Center Verum ( Site 0900)	Kyiv		Ukraine	03040
72	GI Institute of POG of NAMS of Ukraine ( Site 0905)	Kyiv		Ukraine	03067
73	City Clinical Hospital No. 9 ( Site 0901)	Kyiv		Ukraine	04112
74	Multiprofile medical center on the base of Odessa National Medical University ( Site 0908)	Odessa		Ukraine	65023
75	Communal not commercial institution. Ternopil City Community Hospital 2 ( Site 0903)	Ternopil		Ukraine	46400
76	Communal Nonprofit Enterprize Maternity Hospital 4 ( Site 0904)	Zaporizhzhya		Ukraine	69065
77	Communal Institution Maternity Hospital 3 ( Site 0909)	Zaporizhzhya		Ukraine	69071
78	Municipal Institution Zaporizhzhya Regional Clinical Hospital ( Site 0906)	Zaporizhzhya		Ukraine	69071

Sponsors and Collaborators

• Merck Sharp & Dohme LLC

Investigators

• Study Director: Medical Director, Merck Sharp & Dohme LLC

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - May 9, 2018

More Information

Publications

None provided.

• Responsible Party: Merck Sharp & Dohme LLC
• ClinicalTrials.gov Identifier: NCT03654326
• Other Study ID Numbers: 7264-034; 2018-001098-26; MK-7264-034
• First Posted: Aug 31, 2018
• Last Update Posted: Jul 7, 2021
• Last Verified: Jun 1, 2021

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Endometriosis; Naproxen

Study Results

Participant Flow

Pre-assignment Detail	This study included a baseline menstrual cycle (approximately 4 weeks) prior to randomization to either gefapixant or placebo.

Arm/Group Title	Gefapixant	Placebo
Arm/Group Description	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.	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.
Period Title: Overall Study
STARTED	94	93
COMPLETED	88	87
NOT COMPLETED	6	6

Baseline Characteristics

Arm/Group Title	Gefapixant	Placebo	Total
Arm/Group Description	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.	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.	Total of all reporting groups
Overall Participants	94	93	187
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	34.5 (6.6)	34.8 (7.3)	34.6 (6.9)
Sex: Female, Male (Count of Participants)
Female	94 100%	93 100%	187 100%
Male	0 0%	0 0%	0 0%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	35 37.2%	31 33.3%	66 35.3%
Not Hispanic or Latino	59 62.8%	62 66.7%	121 64.7%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	1 1.1%	0 0%	1 0.5%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	4 4.3%	3 3.2%	7 3.7%
White	88 93.6%	86 92.5%	174 93%
More than one race	1 1.1%	4 4.3%	5 2.7%
Unknown or Not Reported	0 0%	0 0%	0 0%
Average Daily Pelvic Pain Score (Scores on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Scores on a scale]	6.5 (1.0)	6.5 (1.0)	6.5 (1.0)

Outcome Measures

1. Primary Outcome

Title	Change From Baseline in Average Daily Pelvic Pain Score During Treatment Cycle 2
Description	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)

Outcome Measure Data

Analysis Population Description

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/Group Title	Gefapixant	Placebo
Arm/Group Description	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.	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.
Measure Participants	94	93
Least Squares Mean (95% Confidence Interval) [Scores on a Scale]	-2.2	-1.7

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Gefapixant, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.066
	Comments	Based on the longitudinal analysis of covariance (ANCOVA) model including factors for average pelvic pain scores at baseline cycle, stratum, treatment, cycle, interaction of stratum-by-cycle, and the interaction of treatment-by-cycle as covariates
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Difference in Least Squares Mean
	Estimated Value	-0.5
	Confidence Interval	(2-Sided) 95%; -1.01 to 0.03
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Primary Outcome

Title	Percentage of Participants Who Experienced an Adverse Event
Description	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

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least one dose of study intervention.

Arm/Group Title	Gefapixant	Placebo
Arm/Group Description	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.	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.
Measure Participants	94	93
Number [Percentage of Participants]	53.2 56.6%	35.5 38.2%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Gefapixant, Placebo
	Comments
	Type of Statistical Test	Other
	Comments	Difference in percentage of participants who experienced one or more adverse events
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference in % vs Placebo
	Estimated Value	17.7
	Confidence Interval	(2-Sided) 95%; 3.4 to 31.3
	Parameter Dispersion	Type: Value:
	Estimation Comments	Based on Miettinen & Nurminen method

3. Primary Outcome

Title	Percentage of Participants Who Discontinued Study Drug Due to an Adverse Event
Description	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

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least one dose of study intervention.

Arm/Group Title	Gefapixant	Placebo
Arm/Group Description	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.	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.
Measure Participants	94	93
Number [Percentage of Participants]	3.2 3.4%	0.0 0%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Gefapixant, Placebo
	Comments
	Type of Statistical Test	Other
	Comments	Difference in percentage of participants who discontinued study drug due to an adverse event
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference in % vs Placebo
	Estimated Value	3.2
	Confidence Interval	(2-Sided) 95%; -0.9 to 9.0
	Parameter Dispersion	Type: Value:
	Estimation Comments	Based on Miettinen & Nurminen method

4. Secondary Outcome

Title	Change From Baseline in Average Daily Cyclic Pelvic Pain Score During Treatment Cycle 2
Description	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)

Outcome Measure Data

Analysis Population Description

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/Group Title	Gefapixant	Placebo
Arm/Group Description	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.	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.
Measure Participants	89	90
Least Squares Mean (95% Confidence Interval) [Scores on a Scale]	-2.0	-1.3

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Gefapixant, Placebo
	Comments
	Type of Statistical Test	Other
	Comments	The difference in least squares mean was based on the longitudinal analysis of covariance (ANCOVA) model including factors for average pelvic pain scores at baseline cycle, stratum, treatment, cycle, interaction of stratum-by-cycle, and the interaction of treatment-by-cycle as covariates
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference in Least Squares Mean
	Estimated Value	-0.6
	Confidence Interval	(2-Sided) 95%; -1.18 to -0.06
	Parameter Dispersion	Type: Value:
	Estimation Comments

5. Secondary Outcome

Title	Change From Baseline in Average Daily Non-Cyclic Pelvic Pain Score During Treatment Cycle 2
Description	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)

Outcome Measure Data

Analysis Population Description

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/Group Title	Gefapixant	Placebo
Arm/Group Description	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.	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.
Measure Participants	91	90
Least Squares Mean (95% Confidence Interval) [Scores on a Scale]	-2.3	-1.8

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Gefapixant, Placebo
	Comments
	Type of Statistical Test	Other
	Comments	The difference in least squares mean was based on the longitudinal analysis of covariance (ANCOVA) model including factors for average pelvic pain scores at baseline cycle, stratum, treatment, cycle, interaction of stratum-by-cycle, and the interaction of treatment-by-cycle as covariates
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference in Least Squares Mean
	Estimated Value	-0.5
	Confidence Interval	(2-Sided) 95%; -1.04 to 0.03
	Parameter Dispersion	Type: Value:
	Estimation Comments

Adverse Events

Time Frame	All-cause mortality: Up to approximately 24 weeks Serious adverse events and other adverse events: Up to approximately 12 weeks
Adverse Event Reporting Description	All randomized participants who received at least one dose of study intervention
Arm/Group Title	Gefapixant		Placebo
Arm/Group Description	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.		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.
All Cause Mortality
	Gefapixant		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/94 (0%)		0/93 (0%)
Serious Adverse Events
	Gefapixant		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/94 (0%)		0/93 (0%)
Other (Not Including Serious) Adverse Events
	Gefapixant		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	36/94 (38.3%)		12/93 (12.9%)
Gastrointestinal disorders
Diarrhoea	6/94 (6.4%)	6	0/93 (0%)	0
Dry mouth	6/94 (6.4%)	6	2/93 (2.2%)	2
Nervous system disorders
Ageusia	9/94 (9.6%)	9	1/93 (1.1%)	1
Dysgeusia	15/94 (16%)	16	2/93 (2.2%)	2
Headache	4/94 (4.3%)	4	7/93 (7.5%)	7
Hypogeusia	5/94 (5.3%)	5	0/93 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

If publication activity is not directed by the Sponsor, the investigator agrees to submit all manuscripts or abstracts to the Sponsor before submission.