Diabetic Peripheral Neuropathic Pain
Conditions
Brief summary
To evaluate the efficacy of NYX-2925 versus placebo in treating the neuropathic pain associated with diabetic peripheral neuropathy.
Detailed description
This is a randomized, double-blind, placebo-controlled study to assess the efficacy and safety of NYX-2925 in subjects with neuropathic pain associated with diabetic peripheral neuropathy. The study will be a 13- to 16-week study, including a 1- to 4-week Screening Period, followed by a 12- week double-blind, randomized, placebo-controlled Treatment Period.
Interventions
DRUGNYX-2925 50 mg
NYX-2925 administered orally
DRUGPlacebo
Placebo administered orally
Sponsors
Worldwide Clinical Trials
Aptinyx
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Masking description
Randomization algorithm, randomization allocation, allocation to study drug or placebo.
Intervention model description
Subjects will be randomized to receive either placebo or NYX-2925.
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Informed consent * Subject has diabetic peripheral neuropathy of symmetrical nature in lower extremities for ≥4 years and reports at least moderate pain over the last week * Stable diabetic and protocol allowed medication during the study * Agrees to use highly effective birth control during the study * Has not participated in an interventional study for at least 30 days and agrees not to participate in another interventional study during the study
Exclusion criteria
* Pain due to other conditions or diseases that would complicate participation in the study or pain reporting * Current or historical serious medical conditions * Prior participation in NYX-2925 clinical trial
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Pain Intensity Numeric Rating Scale (NRS) Score | Week 12 | Change from baseline in the weekly mean of the daily Numeric Rating Scale (NRS) score assessing average pain intensity related to DPN in the past 24 hours. In the NRS, a participant selects a whole number (0 to 10) that best indicates the intensity of his/her pain, where 0 represents no pain and 10 represents worst pain imaginable. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Patient Global Impression of Change (PGI-C) | Week 12 | Number of subjects 'much improved' or 'very much improved' on Patient Global Impression of Change (PGI-C) |
| Number of Subjects Achieving ≥30% Pain Reduction | Week 12 | Number of subjects achieving ≥30% pain reduction from baseline in the weekly mean NRS average pain intensity related to DPN |
| Daily Sleep Interference Scale (DSIS) Score | Week 12 | Change from baseline in the weekly mean of the Daily Sleep Interference Scale (DSIS) scores. The DSIS asks participants to ''Select the number that best describes how much your pain has interfered with your sleep during the past 24 hours.'' Response options for the DSIS range from 0 (did not interfere with sleep) to 10 (completely interfered with sleep/unable to sleep due to pain). |
| Norfolk Quality of Life Questionnaire - Diabetic Neuropathy (QOL-DN) Score | Week 12 | Change from baseline in the Norfolk Quality of Life Questionnaire - Diabetic Neuropathy (QOL-DN) score. The QOL-DN is a 47 item subject reported questionnaire. Scores range from 0-126, and lower scores indicate improved quality of life. |
| Use of Rescue Medication | Week 12 | Number of subjects using rescue medication |
| Number of Subjects Achieving ≥50% Reduction | Week 12 | Number of subjects achieving ≥50% reduction from baseline in the weekly mean NRS average pain intensity related to DPN |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| NYX-2925 NYX-2925 50 mg QD
NYX-2925 50 mg: NYX-2925 administered orally | 114 |
| Placebo Placebo QD
Placebo: Placebo administered orally | 114 |
| Total | 228 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 5 | 8 |
| Overall Study | Lack of Efficacy | 3 | 2 |
| Overall Study | Lost to Follow-up | 0 | 1 |
| Overall Study | Non-compliance | 5 | 4 |
| Overall Study | Randomized in error | 1 | 2 |
| Overall Study | Withdrawal by Subject | 3 | 5 |
Baseline characteristics
| Characteristic | NYX-2925 | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 61.7 years STANDARD_DEVIATION 7.73 | 60.0 years STANDARD_DEVIATION 8.63 | 60.8 years STANDARD_DEVIATION 8.22 |
| Duration of DPN at Baseline (Years) | 8.593 years STANDARD_DEVIATION 4.3059 | 8.701 years STANDARD_DEVIATION 4.1238 | 8.647 years STANDARD_DEVIATION 4.2065 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 42 Participants | 47 Participants | 89 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 72 Participants | 67 Participants | 139 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 3 Participants | 4 Participants | 7 Participants |
| Race (NIH/OMB) Black or African American | 21 Participants | 27 Participants | 48 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants | 3 Participants | 5 Participants |
| Race (NIH/OMB) White | 86 Participants | 80 Participants | 166 Participants |
| Region of Enrollment United States | 114 participants | 114 participants | 228 participants |
| Sex: Female, Male Female | 49 Participants | 51 Participants | 100 Participants |
| Sex: Female, Male Male | 65 Participants | 63 Participants | 128 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 114 | 2 / 114 |
| other Total, other adverse events | 15 / 114 | 15 / 114 |
| serious Total, serious adverse events | 1 / 114 | 6 / 114 |
Outcome results
Primary
Pain Intensity Numeric Rating Scale (NRS) Score
Change from baseline in the weekly mean of the daily Numeric Rating Scale (NRS) score assessing average pain intensity related to DPN in the past 24 hours. In the NRS, a participant selects a whole number (0 to 10) that best indicates the intensity of his/her pain, where 0 represents no pain and 10 represents worst pain imaginable.
Time frame: Week 12
Population: Modified Intent to Treat Population includes all subjects who received at least one dose of study drug with at least one post-baseline assessment of the pain intensity NRS
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| NYX-2925 | Pain Intensity Numeric Rating Scale (NRS) Score | -2.01 units on a scale | Standard Deviation 1.821 |
| Placebo | Pain Intensity Numeric Rating Scale (NRS) Score | -2.27 units on a scale | Standard Deviation 2.102 |
p-value: 0.704t-test, 2 sided
Secondary
Daily Sleep Interference Scale (DSIS) Score
Change from baseline in the weekly mean of the Daily Sleep Interference Scale (DSIS) scores. The DSIS asks participants to ''Select the number that best describes how much your pain has interfered with your sleep during the past 24 hours.'' Response options for the DSIS range from 0 (did not interfere with sleep) to 10 (completely interfered with sleep/unable to sleep due to pain).
Time frame: Week 12
Population: Population Description: Modified Intent to Treat Population includes all subjects who received at least one dose of study drug with at least one post-baseline assessment of the pain intensity NRS
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| NYX-2925 | Daily Sleep Interference Scale (DSIS) Score | -2.11 units on a scale | Standard Deviation 1.903 |
| Placebo | Daily Sleep Interference Scale (DSIS) Score | -2.39 units on a scale | Standard Deviation 2.344 |
p-value: 0.684t-test, 2 sided
Secondary
Norfolk Quality of Life Questionnaire - Diabetic Neuropathy (QOL-DN) Score
Change from baseline in the Norfolk Quality of Life Questionnaire - Diabetic Neuropathy (QOL-DN) score. The QOL-DN is a 47 item subject reported questionnaire. Scores range from 0-126, and lower scores indicate improved quality of life.
Time frame: Week 12
Population: Population Description: Modified Intent to Treat Population includes all subjects who received at least one dose of study drug with at least one post-baseline assessment of the pain intensity NRS
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| NYX-2925 | Norfolk Quality of Life Questionnaire - Diabetic Neuropathy (QOL-DN) Score | -15.3 units on a scale | Standard Deviation 17.91 |
| Placebo | Norfolk Quality of Life Questionnaire - Diabetic Neuropathy (QOL-DN) Score | -16.7 units on a scale | Standard Deviation 21.14 |
p-value: 0.273t-test, 2 sided
Secondary
Number of Subjects Achieving ≥30% Pain Reduction
Number of subjects achieving ≥30% pain reduction from baseline in the weekly mean NRS average pain intensity related to DPN
Time frame: Week 12
Population: Population Description: Modified Intent to Treat Population includes all subjects who received at least one dose of study drug with at least one post-baseline assessment of the pain intensity NRS
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| NYX-2925 | Number of Subjects Achieving ≥30% Pain Reduction | 51 Participants |
| Placebo | Number of Subjects Achieving ≥30% Pain Reduction | 52 Participants |
p-value: 0.483t-test, 2 sided
Secondary
Number of Subjects Achieving ≥50% Reduction
Number of subjects achieving ≥50% reduction from baseline in the weekly mean NRS average pain intensity related to DPN
Time frame: Week 12
Population: Population Description: Modified Intent to Treat Population includes all subjects who received at least one dose of study drug with at least one post-baseline assessment of the pain intensity NRS
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| NYX-2925 | Number of Subjects Achieving ≥50% Reduction | 29 Participants |
| Placebo | Number of Subjects Achieving ≥50% Reduction | 35 Participants |
p-value: 0.199t-test, 2 sided
Secondary
Patient Global Impression of Change (PGI-C)
Number of subjects 'much improved' or 'very much improved' on Patient Global Impression of Change (PGI-C)
Time frame: Week 12
Population: Population Description: Modified Intent to Treat Population includes all subjects who received at least one dose of study drug with at least one post-baseline assessment of the pain intensity NRS
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| NYX-2925 | Patient Global Impression of Change (PGI-C) | 38 Participants |
| Placebo | Patient Global Impression of Change (PGI-C) | 40 Participants |
p-value: 0.743t-test, 2 sided
Secondary
Use of Rescue Medication
Number of subjects using rescue medication
Time frame: Week 12
Population: Population Description: Modified Intent to Treat Population includes all subjects who received at least one dose of study drug with at least one post-baseline assessment of the pain intensity NRS
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| NYX-2925 | Use of Rescue Medication | 100 Participants |
| Placebo | Use of Rescue Medication | 97 Participants |
p-value: 0.668t-test, 2 sided