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The Safety and Efficacy of Gefapixant (AF-219/MK-7264) in Female Participants With Interstitial Cystitis /Bladder Pain Syndrome (MK-7264-005)

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ClinicalTrials.gov Identifier: NCT01569438
Recruitment Status : Terminated
First Posted : April 3, 2012
Results First Posted : January 12, 2017
Last Update Posted : August 17, 2020
Sponsor:
Information provided by (Responsible Party):
Afferent Pharmaceuticals, Inc.

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Condition Bladder Pain Syndrome
Interventions Drug: Gefapixant
Drug: Placebo
Enrollment 107
Recruitment Details Overall, 107 participants were randomized (55 in Gefapixant intervention group, and 52 in Placebo group).
Pre-assignment Details Of 107 participants randomized to the study, 105 received at least one dose of study treatment (All Treated Population) and were evaluable for all safety analysis.
Arm/Group Title Placebo Gefapixant
Hide Arm/Group Description Female participants receive dose matched placebo tablets, twice daily (BID), orally, with food for 4 weeks. Female participants receive gefapixant, a total dose titrated from 50 mg to highest tolerated dose (maximum of 300 mg) twice daily (BID), orally over a period of 6 days with food depending on safety and tolerability, and then maintain that dose for the course of a 4-week treatment period. Participants were allowed to decrease the dose if tolerability issues occurred.
Period Title: Overall Study
Started 52 55
Treated 51 54
Titration Set 38 36
Completed 45 33
Not Completed 7 22
Reason Not Completed
Lack of Efficacy             1             2
Withdrawal by Subject             0             3
Adverse Event             2             15
Protocol Violation             2             0
Decrease of GFR greater than 30 ml/min             1             0
Sponsor/Physician decision             1             1
Unable to adhere to study schedule             0             1
Arm/Group Title Gefapixant Placebo Total
Hide Arm/Group Description Female participants receive gefapixant, a total dose titrated from 50 mg to highest tolerated dose (maximum of 300 mg) twice daily (BID), orally over a period of 6 days with food depending on safety and tolerability, and then maintain that dose for the course of a 4-week treatment period. Participants were allowed to decrease the dose if tolerability issues occurred. Female participants receive dose matched placebo tablets, twice daily (BID), orally, with food for 4 weeks. Total of all reporting groups
Overall Number of Baseline Participants 55 52 107
Hide Baseline Analysis Population Description
All randomized participants
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 55 participants 52 participants 107 participants
<=18 years
0
   0.0%
0
   0.0%
0
   0.0%
Between 18 and 65 years
50
  90.9%
52
 100.0%
102
  95.3%
>=65 years
5
   9.1%
0
   0.0%
5
   4.7%
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 55 participants 52 participants 107 participants
Female
55
 100.0%
52
 100.0%
107
 100.0%
Male
0
   0.0%
0
   0.0%
0
   0.0%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 55 participants 52 participants 107 participants
Hispanic or Latino
3
   5.5%
0
   0.0%
3
   2.8%
Not Hispanic or Latino
52
  94.5%
52
 100.0%
104
  97.2%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 55 participants 52 participants 107 participants
American Indian or Alaska Native
2
   3.6%
0
   0.0%
2
   1.9%
Asian
0
   0.0%
0
   0.0%
0
   0.0%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
5
   9.1%
6
  11.5%
11
  10.3%
White
46
  83.6%
46
  88.5%
92
  86.0%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
2
   3.6%
0
   0.0%
2
   1.9%
Region of Enrollment  
Measure Type: Count of Participants
Unit of measure:  Participants
United States Number Analyzed 55 participants 52 participants 107 participants
55
 100.0%
52
 100.0%
107
 100.0%
Numeric Pain Rating Scale (NPRS) Score   [1] [2] 
Mean (Standard Deviation)
Unit of measure:  Score on a scale
Number Analyzed 54 participants 51 participants 105 participants
6.20  (1.41) 6.53  (1.23) 6.36  (1.33)
[1]
Measure Description: Participants were instructed to select a number between 0 and 10 where 0 is no pain and 10 is the worst pain possible. The scale was completed by telephone (an interactive voice response system [IVRS]) every evening before bedtime. In order to qualify for study entry, participants must have had an average score of >=4 and <10 during the baseline assessment phase.
[2]
Measure Analysis Population Description: NPRS score was calculated only on randomized participants who received at least had one dose of study treatment.
1.Primary Outcome
Title Change From Baseline in the Average Mean Numeric Pain Rating Scale (NPRS) Score at Week 4
Hide Description The bladder pain severity was measured using 0-10 NPRS, with 0 representing 'no pain' and 10 representing 'the worst pain possible'. Participants were asked to select a number on the scale that best described the severity of bladder pain during past 24 hours over telephone using an interactive voice response system (IVRS) every evening at bedtime during the baseline assessment phase and treatment phase (up to 4 weeks). The primary analysis was conducted using a Mixed Model with Repeated Measures (MMRM) approach to calculate the Least Squares (LS) mean change from baseline in NPRS score and associated Standard Error (SE) at Week 4 for each treatment arm. Negative values indicate decrease in bladder pain severity.
Time Frame Baseline and Week 4
Hide Outcome Measure Data
Hide Analysis Population Description
Titration Completers Population - defined as participants who received at least 1 dose of drug, had at least 1 post-baseline NPRS Score, who titrated the dose in Week 1 of the treatment phase, and who completed the 4-week treatment phase
Arm/Group Title Gefapixant Placebo
Hide Arm/Group Description:
Female participants receive gefapixant, a total dose titrated from 50 mg to highest tolerated dose (maximum of 300 mg) twice daily (BID), orally over a period of 6 days with food depending on safety and tolerability, and then maintain that dose for the course of a 4-week treatment period. Participants were allowed to decrease the dose if tolerability issues occurred.
Female participants receive dose matched placebo tablets, twice daily (BID), orally, with food for 4 weeks.
Overall Number of Participants Analyzed 26 35
Least Squares Mean (Standard Error)
Unit of Measure: Score on a scale
-2.6  (0.34) -1.9  (0.31)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Gefapixant, Placebo
Comments MMRM approach was used to model the change from baseline as a function of treatment, week, treatment by week interaction, baseline score, and baseline score by week interaction.
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0734
Comments one-sided
Method Mixed Model with Repeated Measures
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference
Estimated Value -0.7
Confidence Interval (2-Sided) 90%
-1.6 to 0.2
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Change From Baseline in Painful Bladder/Interstitial Cystitis Symptom Diary (PBIC-SD) Score at Week 4
Hide Description To assess the severity of bladder pain syndrome (BPS), an 8-item participant self-report PBIC-SD measure was used. Participants were asked to select a number on the scale that best described the severity of bladder pain over telephone using an IVRS each evening on the three consecutive days (during the Baseline Assessment Phase and during each Treatment Week up to 4 weeks). Each item was graded on a scale from 0 (good condition) to 4 (poor condition) with a total score range 0-32. Higher scores indicate more severe BPS. The analysis was conducted using a MMRM approach to calculate the LS mean change from baseline PBIC-SD total score and associated SE at Week 4 for each treatment arm. Negative values indicate decrease in severity of BPS.
Time Frame Baseline and Week 4
Hide Outcome Measure Data
Hide Analysis Population Description
Titration Completers Population - defined as participants who received at least 1 dose of drug, had at least 1 post-baseline PBIC-SD Score, who titrated the dose in Week 1 of the treatment phase, and who completed the 4-week treatment phase.
Arm/Group Title Gefapixant Placebo
Hide Arm/Group Description:
Female participants receive gefapixant, a total dose titrated from 50 mg to highest tolerated dose (maximum of 300 mg) twice daily (BID), orally over a period of 6 days with food depending on safety and tolerability, and then maintain that dose for the course of a 4-week treatment period. Participants were allowed to decrease the dose if tolerability issues occurred.
Female participants receive dose matched placebo tablets, twice daily (BID), orally, with food for 4 weeks.
Overall Number of Participants Analyzed 27 36
Least Squares Mean (Standard Error)
Unit of Measure: Score on a scale
-7.8  (1.29) -6.7  (1.15)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Gefapixant, Placebo
Comments MMRM approach was used to model the change from baseline as a function of treatment, week, treatment by week interaction, baseline score, and baseline score by week interaction.
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2726
Comments one-sided
Method Mixed Model With Repeated Measures
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference
Estimated Value -1.0
Confidence Interval (2-Sided) 90%
-3.9 to 1.8
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Change From Baseline in O'Leary-Sant Interstitial Cystitis Symptom Index (ICSI) Score at Week 4
Hide Description To measure the severity of BPS (urgency and frequency of urination, nighttime urination, and pain or burning) over past month, a 4-item self-report ICSI measure was used. Participants were asked to select a number on the scale that best described the severity of symptoms over telephone using an IVRS every evening at bedtime during the baseline assessment phase and treatment phase (up to 4 weeks). The ICSI score range from 0 (Not at all) to 5 (Almost always) for the first 3 items and a score of 0 (Not at all) to 4 (Almost always) for the last item, with an index score range of 0-19. Higher scores indicate more severe BPS. The analysis was conducted using one-way ANCOVA model to calculate the LS mean change from baseline ICSI total score and associated SE at Week 4 for each treatment arm. Negative values indicate decrease in severity of BPS.
Time Frame Baseline and Week 4
Hide Outcome Measure Data
Hide Analysis Population Description
Titration Completers Population - defined as participants who received at least 1 dose of drug, had at least 1 post-baseline ICSI Score, who titrated the dose in Week 1 of the treatment phase, and who completed the 4-week treatment phase.
Arm/Group Title Gefapixant Placebo
Hide Arm/Group Description:
Female participants receive gefapixant, a total dose titrated from 50 mg to highest tolerated dose (maximum of 300 mg) twice daily (BID), orally over a period of 6 days with food depending on safety and tolerability, and then maintain that dose for the course of a 4-week treatment period. Participants were allowed to decrease the dose if tolerability issues occurred.
Female participants receive dose matched placebo tablets, twice daily (BID), orally, with food for 4 weeks.
Overall Number of Participants Analyzed 35 38
Least Squares Mean (Standard Error)
Unit of Measure: Score on a scale
-3.8  (0.62) -3.4  (0.60)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Gefapixant, Placebo
Comments The one-way ANCOVA model was used to calculate change from baseline as a function of treatment and baseline score.
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3603
Comments one-sided
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference
Estimated Value -0.3
Confidence Interval (2-Sided) 90%
-1.7 to 1.1
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Change From Baseline in Genitourinary Pain Index (GUPI) Score at Week 4
Hide Description To measure the degree of genitourinary pain symptoms, an 8-item self-report GUPI measure was used. Participants were asked to select a number on the scale that best described the severity of symptoms over telephone using an IVRS every evening at bedtime during the baseline assessment phase and treatment phase (up to 4 weeks). The GUPI instrument yields a total score of 0-45 and 3 subscales: pain (score = 0-23), urinary (score = 0-10), and quality of life (score = 0-12). Higher scores indicate more severe symptoms. The analysis was conducted using one-way ANCOVA model to calculate the LS mean change from baseline GUPI total score and associated SE at Week 4 for each treatment arm. Negative values indicate decrease in degree of genitourinary pain symptoms.
Time Frame Baseline and Week 4
Hide Outcome Measure Data
Hide Analysis Population Description
Titration Completers Population - defined as participants who received at least 1 dose of drug, had at least 1 post-baseline GUPI Score, who titrated the dose in Week 1 of the treatment phase, and who completed the 4-week treatment phase.
Arm/Group Title Gefapixant Placebo
Hide Arm/Group Description:
Female participants receive gefapixant, a total dose titrated from 50 mg to highest tolerated dose (maximum of 300 mg) twice daily (BID), orally over a period of 6 days with food depending on safety and tolerability, and then maintain that dose for the course of a 4-week treatment period. Participants were allowed to decrease the dose if tolerability issues occurred.
Female participants receive dose matched placebo tablets, twice daily (BID), orally, with food for 4 weeks.
Overall Number of Participants Analyzed 34 36
Least Squares Mean (Standard Error)
Unit of Measure: Score on a scale
-5.1  (0.88) -3.7  (0.86)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Gefapixant, Placebo
Comments The one-way ANCOVA model was used to calculate change from baseline as a function of treatment and baseline score.
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1183
Comments one-sided
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference
Estimated Value -1.5
Confidence Interval (2-Sided) 90%
-3.5 to 0.6
Estimation Comments [Not Specified]
Time Frame Up to approximately 6 weeks
Adverse Event Reporting Description All-Cause Mortality reported for all randomized participants. Serious Adverse Events (SAEs) and Other Adverse Events (AEs) were reported for all participants who received at least 1 dose of study treatment.
 
Arm/Group Title Placebo Gefapixant
Hide Arm/Group Description Female participants receive dose matched placebo tablets, twice daily (BID), orally, with food for 4 weeks. Female participants receive gefapixant, a total dose titrated from 50 mg to highest tolerated dose (maximum of 300 mg) twice daily (BID), orally over a period of 6 days with food depending on safety and tolerability, and then maintain that dose for the course of a 4-week treatment period. Participants were allowed to decrease the dose if tolerability issues occurred.
All-Cause Mortality
Placebo Gefapixant
Affected / at Risk (%) Affected / at Risk (%)
Total   0/52 (0.00%)   0/55 (0.00%) 
Hide Serious Adverse Events
Placebo Gefapixant
Affected / at Risk (%) Affected / at Risk (%)
Total   0/51 (0.00%)   0/54 (0.00%) 
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Placebo Gefapixant
Affected / at Risk (%) Affected / at Risk (%)
Total   36/51 (70.59%)   53/54 (98.15%) 
Gastrointestinal disorders     
Nausea  1  10/51 (19.61%)  10/54 (18.52%) 
Dry mouth  1  2/51 (3.92%)  7/54 (12.96%) 
Paraesthesia oral  1  0/51 (0.00%)  7/54 (12.96%) 
Salivary hypersecretion  1  0/51 (0.00%)  6/54 (11.11%) 
Vomiting  1  1/51 (1.96%)  5/54 (9.26%) 
Hypoaesthesia oral  1  3/51 (5.88%)  3/54 (5.56%) 
Diarrhoea  1  1/51 (1.96%)  3/54 (5.56%) 
Abdominal pain  1  0/51 (0.00%)  3/54 (5.56%) 
Infections and infestations     
Urinary tract infection  1  1/51 (1.96%)  3/54 (5.56%) 
Investigations     
Urine output decreased  1  1/51 (1.96%)  7/54 (12.96%) 
Metabolism and nutrition disorders     
Decreased appetite  1  0/51 (0.00%)  7/54 (12.96%) 
Musculoskeletal and connective tissue disorders     
Flank pain  1  7/51 (13.73%)  2/54 (3.70%) 
Arthralgia  1  3/51 (5.88%)  0/54 (0.00%) 
Nervous system disorders     
Dysgeusia  1  9/51 (17.65%)  38/54 (70.37%) 
Headache  1  6/51 (11.76%)  5/54 (9.26%) 
Ageusia  1  0/51 (0.00%)  7/54 (12.96%) 
Hypogeusia  1  0/51 (0.00%)  3/54 (5.56%) 
Renal and urinary disorders     
Pollakiuria  1  3/51 (5.88%)  5/54 (9.26%) 
Dysuria  1  1/51 (1.96%)  4/54 (7.41%) 
Bladder pain  1  3/51 (5.88%)  2/54 (3.70%) 
Respiratory, thoracic and mediastinal disorders     
Cough  1  1/51 (1.96%)  7/54 (12.96%) 
Dry throat  1  2/51 (3.92%)  3/54 (5.56%) 
Throat irritation  1  1/51 (1.96%)  3/54 (5.56%) 
1
Term from vocabulary, MedDRA 14.0
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
60 days prior to the submission of any results, the PI shall submit to SPONSOR any proposed PUBLICATION, which period may be extended for an additional 30 days if requested by SPONSOR. If any Confidential Information should be redacted or patent applications relating to an Invention should be filed prior to PUBLICATION, then PUBLICATION will be delayed until patent application has been filed. Delay of a PUBLICATION shall not exceed 24 months from the date of such notice to the PI.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Senior Vice President, Global Clinical Development
Organization: Merck Sharp & Dohme Corp.
Phone: 1-800-672-6372
EMail: ClinicalTrialsDisclosure@merck.com
Layout table for additonal information
Responsible Party: Afferent Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier: NCT01569438    
Other Study ID Numbers: 7264-005
AF219-005 ( Other Identifier: Afferent Pharmaceuticals )
MK-7264-005 ( Other Identifier: Merck Protocol Number )
First Submitted: March 30, 2012
First Posted: April 3, 2012
Results First Submitted: September 23, 2016
Results First Posted: January 12, 2017
Last Update Posted: August 17, 2020