A Four-Week Multicenter Study Evaluating the Safety and Efficacy of Gefapixant (AF-219/MK-7264) in Subjects With Osteoarthritis of the Knee

• Sponsor: Afferent Pharmaceuticals, Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01554579
• Collaborator: (none)
• Enrollment: 171
• Locations: 34
• Arms: 2
• Actual Duration (Months): 19.8
• Patients Per Site: 5
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

The purpose of this study is to assess the efficacy of a single dose level of gefapixant (AF-219/MK-7264) in subjects with moderate to severe pain associated with osteoarthritis (OA) of the knee compared with placebo after 4 weeks of treatment.

The study will also assess the safety and tolerability, changes in physical function, stiffness, treatment response and health outcomes.

Condition or Disease	Intervention/Treatment	Phase
Osteoarthritis of the Knee	Drug: Gefapixant; Drug: Sugar Pill	Phase 2

Detailed Description

Subjects who satisfy entry criteria at Screening will enter the Washout Phase, discontinuing their current nonsteroidal anti-inflammatory drug (NSAID) therapy.

Up to 220 subjects who fulfill flare (and other entry) criteria will be randomized to gefapixant or placebo.

Subjects will complete Treatment Visits 1, 2, 3, and 4 weeks after starting study drug. At each Treatment Visit, subjects will undergo efficacy assessments and safety procedures. During the Washout and Treatment Phases subjects will complete the 'average pain' Numeric Pain Rating Scale (NPRS) and count of rescue medication used for the preceding 24 hours.

Subjects will return 2 weeks after their last Treatment Visit (for a Follow-Up Visit).

Study Design

• Study Type: Interventional
• Actual Enrollment: 171 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Actual Study Start Date: Mar 29, 2012
• Actual Primary Completion Date: Nov 11, 2013
• Actual Study Completion Date: Nov 21, 2013

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Sugar pill	Drug: Sugar Pill; Placebo
Experimental: Gefapixant	Drug: Gefapixant; BID; Other Names: AF-219 MK-7264

Outcome Measures

Primary Outcome Measures

1. The Primary Efficacy Endpoint of This Study is the Weekly Average Daily NPRS (Average Pain) [2 Weeks]

   Subjects were instructed to select a number on a scale that best described their knee arthritis pain during the past 24 hours. The scale was between 0 and 10 where 0 was no pain and 10 was the worst possible pain. The scale was completed by telephone (an interactive voice response system [IVRS]) every evening before bedtime.

Secondary Outcome Measures

1. WOMAC Scores [4 Weeks]

   This is the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). This is a questionnaire that asks subjects to evaluate their pain, stiffness, and physical activities affecting their knee over the past 48 hours. Subjects evaluate their pain, stiffness and physical activities by selecting a number between 0 and 10 where 0 is no pain/no stiffness/no difficulty doing physical activities and 10 is extreme pain/extreme stiffness/extreme difficulty doing physical activities. The questionnaire was administered at Screening, Baseline and at the end of Week 4 by telephone (an interactive voice response system [IVRS]) before bedtime. The scores for each category are totaled (range is 0-100). A lower total score means less pain and a higher total score means greater pain.

2. SF-36 [4 Weeks]

   The SF-36 (acute version 2) was a 36 question survey administered at Baseline and at the end of study or early termination (Week 4). The questionnaire contained numerous domain scores to evaluate physical function, mental function, general health, bodily pain, social functioning and vitality. The question of interest for the analysis was question #1 regarding walking pain. Scores range from 0 - 100. A lower score means decreased pain while walking and a higher score means increased pain while walking.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 40 Years to 80 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Men or women

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

• Men and their female partners must use two forms of birth control

• Clinical and radiographic evidence of chronic knee osteoarthritis

• An average NPRS score of >=5 and <=9 over a 4-7 day washout period of their previous osteoarthritis medications

• Ambulatory

• Have provided written informed consent

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Afferent Investigative Site	Phoenix	Arizona	United States	85018
2	Afferent Investigative Site	Phoenix	Arizona	United States	85027
3	Afferent Investigative Site	San Diego	California	United States	92108
4	Afferent Investigative Site	Clearwater	Florida	United States	33756
5	Afferent Investigative Site	Orlando	Florida	United States	32806
6	Afferent Investigative Site	Pinellas Park	Florida	United States	33781
7	Afferent Investigative Site	Atlanta	Georgia	United States	30329
8	Afferent Investigative Site	Wichita	Kansas	United States	67203
9	Afferent Investigative Site	New Bedford	Massachusetts	United States	02740
10	Afferent Investigative Site	Watertown	Massachusetts	United States	02472
11	Afferent Investigative Site	Troy	Michigan	United States	48098
12	Afferent Investigative Site	Olive Branch	Mississippi	United States	38654
13	Afferent Investigative Site	Hazelwood	Missouri	United States	63042
14	Afferent Investigative Site	Saint Louis	Missouri	United States	63141
15	Afferent Investigative Site	Albuquerque	New Mexico	United States	87102
16	Afferent Investigative Site	Asheville	North Carolina	United States	28803
17	Afferent Investigative Site	Greensboro	North Carolina	United States	27408
18	Afferent Investigative Site	Winston-Salem	North Carolina	United States	27103
19	Afferent Investigative Site	Cincinnati	Ohio	United States	45219
20	Afferent Investigative Site	Toledo	Ohio	United States	43623
21	Afferent Investigative Site	Medford	Oregon	United States	97504
22	Afferent Investigative Site	Duncansville	Pennsylvania	United States	16635
23	Afferent Investigative Site	Warwick	Rhode Island	United States	02886
24	Afferent Investigative Site	Greer	South Carolina	United States	29650
25	Afferent Investigative Site	Mount Pleasant	South Carolina	United States	29464
26	Afferent Investigative Site	Austin	Texas	United States	78705
27	Afferent Investigative Site	Dallas	Texas	United States	75231
28	Afferent Investigative Site	Houston	Texas	United States	77062
29	Afferent Investigative Site	San Antonio	Texas	United States	78209
30	Afferent Investigative Site	San Antonio	Texas	United States	78229
31	Afferent Investigative Site	Clinton	Utah	United States	84015
32	Afferent Investigative Site	Roanoke	Virginia	United States	24018
33	Afferent Investigative Site	Renton	Washington	United States	98057
34	Afferent Investigative Site	Kenosha	Wisconsin	United States	53142

Sponsors and Collaborators

• Afferent Pharmaceuticals, Inc.

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Afferent Pharmaceuticals, Inc.
• ClinicalTrials.gov Identifier: NCT01554579
• Other Study ID Numbers: 7264-004; AF219004
• First Posted: Mar 15, 2012
• Last Update Posted: Jun 27, 2019
• Last Verified: Jun 1, 2019

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Additional relevant MeSH terms: Osteoarthritis; Osteoarthritis, Knee

Study Results

Participant Flow

Arm/Group Title	Sugar Pill	Gefapixant
Arm/Group Description	Sugar Pill: Placebo Subjects in the trial received one tablet twice daily for 4 weeks.	Gefapixant: BID Subjects received one tablet twice daily for 4 weeks.
Period Title: Overall Study
STARTED	86	85
COMPLETED	76	58
NOT COMPLETED	10	27

Baseline Characteristics

Arm/Group Title	Sugar Pill	Gefapixant	Total
Arm/Group Description	Sugar Pill: Placebo	Gefapixant: BID Subjects received one tablet twice daily for 4 weeks.	Total of all reporting groups
Overall Participants	86	85	171
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	64 74.4%	65 76.5%	129 75.4%
>=65 years	22 25.6%	20 23.5%	42 24.6%
Sex: Female, Male (Count of Participants)
Female	52 60.5%	57 67.1%	109 63.7%
Male	34 39.5%	28 32.9%	62 36.3%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	1 1.2%	1 0.6%
Asian	2 2.3%	2 2.4%	4 2.3%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	21 24.4%	20 23.5%	41 24%
White	62 72.1%	62 72.9%	124 72.5%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	1 1.2%	0 0%	1 0.6%
Region of Enrollment (participants) [Number]
United States	86 100%	85 100%	171 100%
Numeric Pain Rating Scale (NPRS) (units on a scale) [Mean (Full Range) ]
Mean (Full Range) [units on a scale]	6.7	6.8	6.75

Outcome Measures

1. Primary Outcome

Title	The Primary Efficacy Endpoint of This Study is the Weekly Average Daily NPRS (Average Pain)
Description	Subjects were instructed to select a number on a scale that best described their knee arthritis pain during the past 24 hours. The scale was between 0 and 10 where 0 was no pain and 10 was the worst possible pain. The scale was completed by telephone (an interactive voice response system [IVRS]) every evening before bedtime.
Time Frame	2 Weeks

Outcome Measure Data

Analysis Population Description

Per protocol population defined as subjects who received at least 1 dose of drug, had at least 1 post-baseline efficacy measure, complied with protocol and did not have major protocol deviations. Compliance with the protocol defined as having (in the last week of the study) a weekly average NPRS score w/ at least 50% non-missing dairy NPRS scores.

Arm/Group Title	Sugar Pill	Gefapixant
Arm/Group Description	Sugar Pill: Placebo Subjects in the trial received one tablet twice daily for 4 weeks.	Gefapixant: BID Subjects received one tablet twice daily for 4 weeks.
Measure Participants	82	74
Mean (Full Range) [units on a scale]	5.3	4.9

2. Secondary Outcome

Title	WOMAC Scores
Description	This is the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). This is a questionnaire that asks subjects to evaluate their pain, stiffness, and physical activities affecting their knee over the past 48 hours. Subjects evaluate their pain, stiffness and physical activities by selecting a number between 0 and 10 where 0 is no pain/no stiffness/no difficulty doing physical activities and 10 is extreme pain/extreme stiffness/extreme difficulty doing physical activities. The questionnaire was administered at Screening, Baseline and at the end of Week 4 by telephone (an interactive voice response system [IVRS]) before bedtime. The scores for each category are totaled (range is 0-100). A lower total score means less pain and a higher total score means greater pain.
Time Frame	4 Weeks

Outcome Measure Data

Analysis Population Description

Per protocol population defined as subjects who received at least 1 dose of drug, had at least 1 post-baseline efficacy measure, complied with protocol and did not have major protocol deviations. Compliance with the protocol defined as having (in the last week of the study) a weekly average NPRS score w/ at least 50% non-missing dairy NPRS scores.

Arm/Group Title	Sugar Pill	Gefapixant
Arm/Group Description	Sugar Pill: Placebo	Gefapixant: BID Subjects received one tablet twice daily for 4 weeks.
Measure Participants	79	71
Mean (Standard Deviation) [units on a scale]	40.7 (23.12)	41.0 (25.26)

3. Secondary Outcome

Title	SF-36
Description	The SF-36 (acute version 2) was a 36 question survey administered at Baseline and at the end of study or early termination (Week 4). The questionnaire contained numerous domain scores to evaluate physical function, mental function, general health, bodily pain, social functioning and vitality. The question of interest for the analysis was question #1 regarding walking pain. Scores range from 0 - 100. A lower score means decreased pain while walking and a higher score means increased pain while walking.
Time Frame	4 Weeks

Outcome Measure Data

Analysis Population Description

Per protocol population defined as subjects who received at least 1 dose of drug, had at least 1 post-baseline efficacy measure, complied with protocol and did not have major protocol deviations. Compliance with the protocol defined as having (in the last week of the study) a weekly average NPRS score w/ at least 50% non-missing dairy NPRS scores.

Arm/Group Title	Sugar Pill	Gefapixant
Arm/Group Description	Sugar Pill: Placebo	Gefapixant: BID Subjects received one tablet twice daily for 4 weeks.
Measure Participants	80	73
Mean (Standard Deviation) [units on a scale]	3.8 (2.39)	4.1 (2.77)

Adverse Events

Arm/Group Title	Sugar Pill		Gefapixant
Arm/Group Description	Sugar Pill: Placebo Subjects in the trial received one tablet twice daily for 4 weeks.		Gefapixant: BID Subjects received one tablet twice daily for 4 weeks.
All Cause Mortality
	Sugar Pill		Gefapixant
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Sugar Pill		Gefapixant
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/86 (1.2%)		0/85 (0%)
Infections and infestations
Bronchitis	1/86 (1.2%)	1	0/85 (0%)	0
Other (Not Including Serious) Adverse Events
	Sugar Pill		Gefapixant
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	17/86 (19.8%)		75/85 (88.2%)
Nervous system disorders
Dysgeusia	4/86 (4.7%)	4	64/85 (75.3%)	64
Ageusia	0/86 (0%)	0	12/85 (14.1%)	12
headache	10/86 (11.6%)	10	9/85 (10.6%)	9
hypogeusia	0/86 (0%)	0	7/85 (8.2%)	7
dizziness	3/86 (3.5%)	3	6/85 (7.1%)	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.