Osteoarthritis of the Knee
Conditions
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.
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).
Interventions
DRUGGefapixant
BID
DRUGSugar Pill
Placebo
Sponsors
Afferent Pharmaceuticals, Inc., a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
40 Years to 80 Years
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Sugar Pill Sugar Pill: Placebo | 86 |
| Gefapixant Gefapixant: BID Subjects received one tablet twice daily for 4 weeks. | 85 |
| Total | 171 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 6 | 25 |
| Overall Study | Lack of Efficacy | 2 | 1 |
| Overall Study | Withdrawal by Subject | 2 | 1 |
Baseline characteristics
| Characteristic | Sugar Pill | Gefapixant | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 22 Participants | 20 Participants | 42 Participants |
| Age, Categorical Between 18 and 65 years | 64 Participants | 65 Participants | 129 Participants |
| Numeric Pain Rating Scale (NPRS) | 6.7 units on a scale | 6.8 units on a scale | 6.75 units on a scale |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 2 Participants | 2 Participants | 4 Participants |
| Race (NIH/OMB) Black or African American | 21 Participants | 20 Participants | 41 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) White | 62 Participants | 62 Participants | 124 Participants |
| Region of Enrollment United States | 86 participants | 85 participants | 171 participants |
| Sex: Female, Male Female | 52 Participants | 57 Participants | 109 Participants |
| Sex: Female, Male Male | 34 Participants | 28 Participants | 62 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 17 / 86 | 75 / 85 |
| serious Total, serious adverse events | 1 / 86 | 0 / 85 |
Outcome results
Primary
The Primary Efficacy Endpoint of This Study is the Weekly Average Daily NPRS (Average Pain)
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
Population: 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 | Measure | Value (MEAN) |
|---|---|---|
| Sugar Pill | The Primary Efficacy Endpoint of This Study is the Weekly Average Daily NPRS (Average Pain) | 5.3 units on a scale |
| Gefapixant | The Primary Efficacy Endpoint of This Study is the Weekly Average Daily NPRS (Average Pain) | 4.9 units on a scale |
Secondary
SF-36
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
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sugar Pill | SF-36 | 3.8 units on a scale | Standard Deviation 2.39 |
| Gefapixant | SF-36 | 4.1 units on a scale | Standard Deviation 2.77 |
Secondary
WOMAC Scores
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
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sugar Pill | WOMAC Scores | 40.7 units on a scale | Standard Deviation 23.12 |
| Gefapixant | WOMAC Scores | 41.0 units on a scale | Standard Deviation 25.26 |