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

• Sponsor: Afferent Pharmaceuticals, Inc. (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT01569438
• Collaborator: (none)
• Enrollment: 107
• Locations: 41
• Arms: 2
• Actual Duration (Months): 25
• Patients Per Site: 2.6
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

The purpose of this study is to assess the efficacy of gefapixant (AF-219/MK-7264) in female participants with moderate to severe pain associated with interstitial cystitis/bladder pain syndrome (IC/BPS) after 4 weeks of treatment.

Condition or Disease	Intervention/Treatment	Phase
Bladder Pain Syndrome	Drug: Gefapixant; Drug: Placebo	Phase 2

Detailed Description

This study is a double-blind, placebo-controlled, randomized trial designed to assess the efficacy and safety of gefapixant in female participants with moderate to severe pain associated with IC/BPS. The study will consist of 4 phases: Screening, Baseline, Treatment, and Follow-up.

Study Design

• Study Type: Interventional
• Actual Enrollment: 107 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Masking Description: Double Blind
• Primary Purpose: Treatment
• Official Title: A Four-Week, Double-Blind, Placebo-Controlled, Randomized, Multicenter Study Evaluating the Safety and Efficacy of AF-219 in Female Subjects With Interstitial Cystitis/Bladder Pain Syndrome (IC/BPS)
• Actual Study Start Date: Apr 13, 2012
• Actual Primary Completion Date: May 1, 2014
• Actual Study Completion Date: May 14, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Gefapixant 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.	Drug: Gefapixant; 50 or 300 mg tablets for a total daily dose of 50, 100, 150, 200, 250 or 300 mg BID, orally with food for 4 weeks; Other Names: AF-219 MK-7264
Placebo Comparator: Placebo Female participants receive dose matched placebo tablets, BID, orally, with food for 4 weeks.	Drug: Placebo; Dose matched placebo tablets, BID, orally, with food for 4 weeks

Outcome Measures

Primary Outcome Measures

1. Change From Baseline in the Average Mean Numeric Pain Rating Scale (NPRS) Score at Week 4 [Baseline and Week 4]

   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.

Secondary Outcome Measures

1. Change From Baseline in Painful Bladder/Interstitial Cystitis Symptom Diary (PBIC-SD) Score at Week 4 [Baseline and Week 4]

   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.

2. Change From Baseline in O'Leary-Sant Interstitial Cystitis Symptom Index (ICSI) Score at Week 4 [Baseline and Week 4]

   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.

3. Change From Baseline in Genitourinary Pain Index (GUPI) Score at Week 4 [Baseline and Week 4]

   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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 80 Years
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Women

• Women of child bearing potential must not be pregnant during the study and must use two forms of birth control

• Clinical evidence of Interstitial Cystitis /Bladder Pain Syndrome (IC/BPS)

• Have provided written informed consent

Exclusion Criteria:

• History of diseases that can be confused for IC/BPS

• Unable to void spontaneously

• Immunosuppressant, intravesicular, nerve stimulator or opioid treatment for certain periods prior to start of the study

• Changes to doses of Elmiron®, antidepressant, alpha-adrenergic antagonist, H1 antagonist, or anti-muscarinic treatment within a certain period prior to the start of the study

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Afferent Investigative Site	Glendale	Alabama	United States	85306
2	Afferent Investigative Site	Homewood	Alabama	United States	35209
3	Afferent Investigative Site	Mobile	Alabama	United States	36608
4	Afferent Investigative Site	Phoenix	Arizona	United States	85018
5	Afferent Investigative Site	Glendora	California	United States	91741
6	Afferent Investigative Site	Murrieta	California	United States	91741
7	Afferent Investigative Site	San Diego	California	United States	92120
8	Afferent Investigative Site	San Diego	California	United States	92123
9	Afferent Investigative Site	Farmington	Connecticut	United States	06032
10	Afferent Investigative Site	New Britain	Connecticut	United States	06052
11	Afferent Investigative Site	Boynton Beach	Florida	United States	33472
12	Afferent Investigative Site	Plantation	Florida	United States	33317
13	Afferent Investigative Site	Coeur d'Alene	Idaho	United States	83814
14	Afferent Investigative Site	Idaho Falls	Idaho	United States	83404
15	Afferent Investigative Site	Meridian	Idaho	United States	83642
16	Afferent Investigative Site	Shreveport	Louisiana	United States	71106
17	Afferent Investigative Site	Annapolis	Maryland	United States	21401
18	Afferent Investigative Site	Ann Arbor	Michigan	United States	48109
19	Afferent Investigative Site	Grand Rapids	Michigan	United States	49503
20	Afferent Investigative Site	Kalamazoo	Michigan	United States	49009
21	Afferent Investigative Site	Royal Oak	Michigan	United States	48073
22	Afferent Investigative Site	Voorhees	New Jersey	United States	08043
23	Afferent Investigative Site	Albuquerque	New Mexico	United States	87109
24	Afferent Investigative Site	Brooklyn	New York	United States	11215
25	Afferent Investigative Site	Hyde Park	New York	United States	11040
26	Afferent Investigative Site	Greenville	North Carolina	United States	27834
27	Afferent Investigative Site	Salisbury	North Carolina	United States	28144
28	Afferent Investigative Site	Winston-Salem	North Carolina	United States	27103
29	Afferent Investigative Site	Cincinnati	Ohio	United States	45212
30	Afferent Investigative Site	Cleveland	Ohio	United States	44109
31	Afferent Investigative Site	Tiffin	Ohio	United States	43351
32	Afferent Investigative Site	Zanesville	Ohio	United States	43701
33	Afferent Investigative Site	Bala-Cynwyd	Pennsylvania	United States	19004
34	Afferent Investigative Site	Lancaster	Pennsylvania	United States	17604
35	Afferent Investigative Site	Myrtle Beach	South Carolina	United States	29572
36	Afferent Investigative Site	Dallas	Texas	United States	75390
37	Afferent Investigative Site	Fort Worth	Texas	United States	76104
38	Afferent Investigative Site	Houston	Texas	United States	77062
39	Afferent Investigative Site	Irving	Texas	United States	75062
40	Afferent Investigative Site	Salt Lake City	Utah	United States	84124
41	Afferent Investigative Site	Virginia Beach	Virginia	United States	23462

Sponsors and Collaborators

• Afferent Pharmaceuticals, Inc.

Investigators

• Study Director: Medical Director, Afferent Pharmaceuticals, Inc.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Afferent Pharmaceuticals, Inc.
• ClinicalTrials.gov Identifier: NCT01569438
• Other Study ID Numbers: 7264-005; AF219-005; MK-7264-005
• First Posted: Apr 3, 2012
• Last Update Posted: Aug 17, 2020
• Last Verified: Aug 1, 2020

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Additional relevant MeSH terms: Cystitis; Cystitis, Interstitial; Syndrome; Somatoform Disorders

Study Results

Participant Flow

Recruitment Details	Overall, 107 participants were randomized (55 in Gefapixant intervention group, and 52 in Placebo group).
Pre-assignment Detail	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
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

Baseline Characteristics

Arm/Group Title	Gefapixant	Placebo	Total
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 Participants	55	52	107
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	50 90.9%	52 100%	102 95.3%
>=65 years	5 9.1%	0 0%	5 4.7%
Sex: Female, Male (Count of Participants)
Female	55 100%	52 100%	107 100%
Male	0 0%	0 0%	0 0%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	3 5.5%	0 0%	3 2.8%
Not Hispanic or Latino	52 94.5%	52 100%	104 97.2%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	2 3.6%	0 0%	2 1.9%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	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%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	2 3.6%	0 0%	2 1.9%
Region of Enrollment (Count of Participants)
United States	55 100%	52 100%	107 100%
Numeric Pain Rating Scale (NPRS) Score (Score on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Score on a scale]	6.20 (1.41)	6.53 (1.23)	6.36 (1.33)

Outcome Measures

1. Primary Outcome

Title	Change From Baseline in the Average Mean Numeric Pain Rating Scale (NPRS) Score at Week 4
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

Outcome Measure Data

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
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.
Measure Participants	26	35
Least Squares Mean (Standard Error) [Score on a scale]	-2.6 (0.34)	-1.9 (0.31)

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
Statistical Test of Hypothesis	p-Value	0.0734
	Comments	one-sided
	Method	Mixed Model with Repeated Measures
	Comments
Method of Estimation	Estimation Parameter	Mean Difference
	Estimated Value	-0.7
	Confidence Interval	(2-Sided) 90%; -1.6 to 0.2
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Change From Baseline in Painful Bladder/Interstitial Cystitis Symptom Diary (PBIC-SD) Score at Week 4
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

Outcome Measure Data

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
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.
Measure Participants	27	36
Least Squares Mean (Standard Error) [Score on a scale]	-7.8 (1.29)	-6.7 (1.15)

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
Statistical Test of Hypothesis	p-Value	0.2726
	Comments	one-sided
	Method	Mixed Model With Repeated Measures
	Comments
Method of Estimation	Estimation Parameter	Mean Difference
	Estimated Value	-1.0
	Confidence Interval	(2-Sided) 90%; -3.9 to 1.8
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Change From Baseline in O'Leary-Sant Interstitial Cystitis Symptom Index (ICSI) Score at Week 4
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

Outcome Measure Data

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
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.
Measure Participants	35	38
Least Squares Mean (Standard Error) [Score on a scale]	-3.8 (0.62)	-3.4 (0.60)

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
Statistical Test of Hypothesis	p-Value	0.3603
	Comments	one-sided
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference
	Estimated Value	-0.3
	Confidence Interval	(2-Sided) 90%; -1.7 to 1.1
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Secondary Outcome

Title	Change From Baseline in Genitourinary Pain Index (GUPI) Score at Week 4
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

Outcome Measure Data

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
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.
Measure Participants	34	36
Least Squares Mean (Standard Error) [Score on a scale]	-5.1 (0.88)	-3.7 (0.86)

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
Statistical Test of Hypothesis	p-Value	0.1183
	Comments	one-sided
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference
	Estimated Value	-1.5
	Confidence Interval	(2-Sided) 90%; -3.5 to 0.6
	Parameter Dispersion	Type: Value:
	Estimation Comments

Adverse Events

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
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 (%)	# Events	Affected / at Risk (%)	# Events
Total	0/52 (0%)		0/55 (0%)
Serious Adverse Events
	Placebo		Gefapixant
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/51 (0%)		0/54 (0%)
Other (Not Including Serious) Adverse Events
	Placebo		Gefapixant
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	36/51 (70.6%)		53/54 (98.1%)
Gastrointestinal disorders
Nausea	10/51 (19.6%)		10/54 (18.5%)
Dry mouth	2/51 (3.9%)		7/54 (13%)
Paraesthesia oral	0/51 (0%)		7/54 (13%)
Salivary hypersecretion	0/51 (0%)		6/54 (11.1%)
Vomiting	1/51 (2%)		5/54 (9.3%)
Hypoaesthesia oral	3/51 (5.9%)		3/54 (5.6%)
Diarrhoea	1/51 (2%)		3/54 (5.6%)
Abdominal pain	0/51 (0%)		3/54 (5.6%)
Infections and infestations
Urinary tract infection	1/51 (2%)		3/54 (5.6%)
Investigations
Urine output decreased	1/51 (2%)		7/54 (13%)
Metabolism and nutrition disorders
Decreased appetite	0/51 (0%)		7/54 (13%)
Musculoskeletal and connective tissue disorders
Flank pain	7/51 (13.7%)		2/54 (3.7%)
Arthralgia	3/51 (5.9%)		0/54 (0%)
Nervous system disorders
Dysgeusia	9/51 (17.6%)		38/54 (70.4%)
Headache	6/51 (11.8%)		5/54 (9.3%)
Ageusia	0/51 (0%)		7/54 (13%)
Hypogeusia	0/51 (0%)		3/54 (5.6%)
Renal and urinary disorders
Pollakiuria	3/51 (5.9%)		5/54 (9.3%)
Dysuria	1/51 (2%)		4/54 (7.4%)
Bladder pain	3/51 (5.9%)		2/54 (3.7%)
Respiratory, thoracic and mediastinal disorders
Cough	1/51 (2%)		7/54 (13%)
Dry throat	2/51 (3.9%)		3/54 (5.6%)
Throat irritation	1/51 (2%)		3/54 (5.6%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

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.