Psoriasis
Conditions
Brief summary
This study was conducted: 1) to assess the clinical effect of Navarixin on the Psoriasis Activity and Severity Index (PASI), 2) to determine the effects of Navarixin on the Physician's Global Assessment (PGA), 3) to evaluate the safety and tolerability of Navarixin, and 4) to determine the multiple-dose pharmacokinetics of Navarixin.
Interventions
DRUGNavarixin 10 mg
Navarixin capsules orally, once daily for 28 days.
OTHERPlacebo
Matching placebo capsules to Navarixin orally, once daily for 28 days.
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* Body Mass Index (BMI) 19 to 34, BMI = weight (kg)/height (m\^2). * Must have a diagnosis of psoriasis vulgaris (PASI \>8) present for at least 1 year. Participants with an on-therapy PASI \<=8 at Screening may be considered for inclusion. Participants must be discussed with the Sponsor prior to enrollment and the subject must have indicated that they are not satisfied with current therapy. To be included, participants must have a PASI \>8 following washout of their current psoriasis therapy. * Target lesion selected must be located on the head, trunk, arms or legs and be at least 10 cm\^2 in size. The lesion's total numerical ratings for erythema, infiltration, and desquamation must be at least 6 out of the possible 12. Severity score for desquamation must be at least 2. * Vital sign measurements (taken after \ 3 minutes in a supine position) must be within the following ranges: oral body temperature between 35.0°C to 37.5°C; systolic blood pressure, 90 to 160 mm Hg; diastolic blood pressure, 45 to 90 mm Hg; pulse rate, 40 to 100 bpm. * Have stable disease (ie, off treatment PASI during Screening period and Baseline PASI should not differ by more than 40%). * Clinical laboratory tests (CBC, blood chemistries, and urinalysis) must be within normal limits or clinically acceptable to the investigator/sponsor. Participants must have a neutrophil count of at least 2 x 10\^9/L to be included. * Free of any clinically significant disease (other than psoriasis). * Willing to give written informed consent and able to adhere to dose and visit schedules. * For female participants: Negative serum pregnancy test (beta-hCG) and urine pregnancy test. Agree to use medically accepted methods of contraception during and for an appropriate pre-study period while receiving protocol specified medication, and for 1 month after stopping medication. Female participants of non-childbearing potential must be surgically sterilized or be postmenopausal. * Male subject must agree to use an adequate form of contraception for the duration of the study. * At Screening, ECG conduction intervals must be within gender specific normal range (ie, QTc for males \<430 msec and females \<450 msec) or if not within the normal range, the values must be considered clinically insignificant by the investigator and sponsor.
Exclusion criteria
* Female participants who are pregnant, intend to become pregnant (within 3 months of ending the study), or are breastfeeding. * Participants who, in the opinion of the investigator, will not be able to participate optimally in the study. * Any surgical or medical condition which might significantly alter the absorption, distribution, metabolism or excretion of any drug. * History of any infectious disease within 4 weeks prior to drug administration and/or are positive for hepatitis B surface antigen, hepatitis C antibodies or human immunodeficiency virus (HIV). * Immunocompromised participants. * Positive screen for drugs with a high potential for abuse or have a history of drug or alcohol abuse in the past 2 years. * History of mental instability or who have been treated for mood disorders. * Donated blood in the past 60 days. * Previous treatment with study medication. * Currently participating in another clinical study or have participated in a clinical study within 30 days. * Part of the study staff personnel or family members of the study staff personnel. * Demonstrated clinically significant (requiring intervention) allergic reactions or who are known to be allergic to components of local anesthetics.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Percent Change From Baseline in the Psoriasis and Activity Severity Index (PASI) Score at Day 29 | Baseline and Day 29 | PASI score is a means to qualify the extent and severity of psoriatic lesions. The total score is calculated as the sum of the extent and severity of lesions on the head, arms, trunk, and legs and the score can range from 0 (no symptoms) to 72 (maximum symptoms). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants by Physician's Assessment of Global Improvement (PGA) Score At Day 29 | Day 29 | The PGA is a questionnaire that asks the treating physician to rate the participant's signs and symptoms on a scale where 0=worse, 1=unchanged, 2= slight improvement, 3= fair improvement, 4= good improvement, 5= excellent improvement, and 6=cleared, with higher scores indicating better outcomes. |
| Mean Maximum Plasma Concentration (Cmax) of Navarixin at Day 28 | Day 28 | Participant blood samples were collected at 0, 0.25, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 10, 12, and 24 hours following oral administration of Navarixin to determine the mean Cmax at Day 28. Blood samples were not collected from the placebo group to evaluate this endpoint. |
| Mean Area Under the Plasma Concentration-Time Curve From Time 0-24 Hours (AUC [0-24]) of Navarixin at Day 28 | Day 28 | Participant blood samples were collected at 0, 0.25, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 10, 12, and 24 hours following oral administration of Navarixin to determine the mean AUC(0-24) at Day 28. Blood samples were not collected from the placebo group to evaluate this endpoint. |
| Mean Terminal Phase Half-life (T1/2) of Navarixin at Day 28 | Day 28 | Participant blood samples were collected at 0, 0.25, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 10, 12, and 24 hours to determine the mean T1/2 of Navarixin following oral administration at Day 28. Blood samples were not collected from the placebo group to evaluate this endpoint. |
| Median Time to Maximum Plasma Concentration (Tmax) of Navarixin at Day 28 | Day 28 | Participant blood samples were collected at 0, 0.25, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 10, 12, and 24 hours following oral administration of Navarixin to determine the Mean Tmax at Day 28. Blood samples were not collected from the placebo group to evaluate this endpoint. |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Navarixin Navarixin 30 mg administered orally once daily for 28 days. | 21 |
| Placebo Matching placebo to Navarixin administered orally once daily for 28 days. | 10 |
| Total | 31 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 0 | 2 |
Baseline characteristics
| Characteristic | Navarixin | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 49.5 Years STANDARD_DEVIATION 10.5 | 43.9 Years STANDARD_DEVIATION 13.4 | 47.7 Years STANDARD_DEVIATION 11.6 |
| Sex: Female, Male Female | 2 Participants | 2 Participants | 4 Participants |
| Sex: Female, Male Male | 19 Participants | 8 Participants | 27 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 12 / 21 | 5 / 10 |
| serious Total, serious adverse events | 0 / 21 | 1 / 10 |
Outcome results
Primary
Mean Percent Change From Baseline in the Psoriasis and Activity Severity Index (PASI) Score at Day 29
PASI score is a means to qualify the extent and severity of psoriatic lesions. The total score is calculated as the sum of the extent and severity of lesions on the head, arms, trunk, and legs and the score can range from 0 (no symptoms) to 72 (maximum symptoms).
Time frame: Baseline and Day 29
Population: The population consisted of all treated participants with follow-up.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Navarixin | Mean Percent Change From Baseline in the Psoriasis and Activity Severity Index (PASI) Score at Day 29 | -3.30 Score on a Scale | Standard Deviation 15.05 |
| Placebo | Mean Percent Change From Baseline in the Psoriasis and Activity Severity Index (PASI) Score at Day 29 | -2.14 Score on a Scale | Standard Deviation 13.26 |
Secondary
Mean Area Under the Plasma Concentration-Time Curve From Time 0-24 Hours (AUC [0-24]) of Navarixin at Day 28
Participant blood samples were collected at 0, 0.25, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 10, 12, and 24 hours following oral administration of Navarixin to determine the mean AUC(0-24) at Day 28. Blood samples were not collected from the placebo group to evaluate this endpoint.
Time frame: Day 28
Population: The population consisted of all enrolled participants for which serum samples were evaluable at Day 28 for AUC (0-24). One participant was excluded due to erroneous blood sample collection relative to Navarixin dosing.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Navarixin | Mean Area Under the Plasma Concentration-Time Curve From Time 0-24 Hours (AUC [0-24]) of Navarixin at Day 28 | 420.37 hr*ng/mL | Standard Deviation 67.57 |
Secondary
Mean Maximum Plasma Concentration (Cmax) of Navarixin at Day 28
Participant blood samples were collected at 0, 0.25, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 10, 12, and 24 hours following oral administration of Navarixin to determine the mean Cmax at Day 28. Blood samples were not collected from the placebo group to evaluate this endpoint.
Time frame: Day 28
Population: The population consisted of all participants for which serum samples were available for the determination of Cmax at Day 28. One participant was excluded due to erroneous blood sample collection relative to Navarixin dosing.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Navarixin | Mean Maximum Plasma Concentration (Cmax) of Navarixin at Day 28 | 209.85 ng/mL | Standard Deviation 51.5 |
Secondary
Mean Terminal Phase Half-life (T1/2) of Navarixin at Day 28
Participant blood samples were collected at 0, 0.25, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 10, 12, and 24 hours to determine the mean T1/2 of Navarixin following oral administration at Day 28. Blood samples were not collected from the placebo group to evaluate this endpoint.
Time frame: Day 28
Population: The population consisted of all enrolled participants for which serum samples were evaluable for T1/2. One participant was excluded due to erroneous blood sample collection relative to Navarixin dosing. An additional 2 participants were excluded from the population because their T1/2 was incalculable.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Navarixin | Mean Terminal Phase Half-life (T1/2) of Navarixin at Day 28 | 13.02 Hours | Standard Deviation 6.63 |
Secondary
Median Time to Maximum Plasma Concentration (Tmax) of Navarixin at Day 28
Participant blood samples were collected at 0, 0.25, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 10, 12, and 24 hours following oral administration of Navarixin to determine the Mean Tmax at Day 28. Blood samples were not collected from the placebo group to evaluate this endpoint.
Time frame: Day 28
Population: The population consisted of all participants for which serum samples were available for the determination of Tmax at Day 28.
| Arm | Measure | Value (MEDIAN) | Dispersion |
|---|---|---|---|
| Navarixin | Median Time to Maximum Plasma Concentration (Tmax) of Navarixin at Day 28 | 0.50 Hours | Full Range 51.5 |
Secondary
Number of Participants by Physician's Assessment of Global Improvement (PGA) Score At Day 29
The PGA is a questionnaire that asks the treating physician to rate the participant's signs and symptoms on a scale where 0=worse, 1=unchanged, 2= slight improvement, 3= fair improvement, 4= good improvement, 5= excellent improvement, and 6=cleared, with higher scores indicating better outcomes.
Time frame: Day 29
Population: The population consisted of all treated participants with follow-up.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Navarixin | Number of Participants by Physician's Assessment of Global Improvement (PGA) Score At Day 29 | Score = 2 (slight improvement) | 8 Participants |
| Navarixin | Number of Participants by Physician's Assessment of Global Improvement (PGA) Score At Day 29 | Score = 4 (good improvement) | 0 Participants |
| Navarixin | Number of Participants by Physician's Assessment of Global Improvement (PGA) Score At Day 29 | Score = 1 (unchanged) | 6 Participants |
| Navarixin | Number of Participants by Physician's Assessment of Global Improvement (PGA) Score At Day 29 | Score = 5 (excellent improvement) | 0 Participants |
| Navarixin | Number of Participants by Physician's Assessment of Global Improvement (PGA) Score At Day 29 | Score = 3 (fair improvement) | 0 Participants |
| Navarixin | Number of Participants by Physician's Assessment of Global Improvement (PGA) Score At Day 29 | Score = 6 (cleared) | 0 Participants |
| Navarixin | Number of Participants by Physician's Assessment of Global Improvement (PGA) Score At Day 29 | Score = 0 (worse) | 7 Participants |
| Placebo | Number of Participants by Physician's Assessment of Global Improvement (PGA) Score At Day 29 | Score = 6 (cleared) | 0 Participants |
| Placebo | Number of Participants by Physician's Assessment of Global Improvement (PGA) Score At Day 29 | Score = 0 (worse) | 2 Participants |
| Placebo | Number of Participants by Physician's Assessment of Global Improvement (PGA) Score At Day 29 | Score = 1 (unchanged) | 2 Participants |
| Placebo | Number of Participants by Physician's Assessment of Global Improvement (PGA) Score At Day 29 | Score = 2 (slight improvement) | 4 Participants |
| Placebo | Number of Participants by Physician's Assessment of Global Improvement (PGA) Score At Day 29 | Score = 3 (fair improvement) | 1 Participants |
| Placebo | Number of Participants by Physician's Assessment of Global Improvement (PGA) Score At Day 29 | Score = 4 (good improvement) | 0 Participants |
| Placebo | Number of Participants by Physician's Assessment of Global Improvement (PGA) Score At Day 29 | Score = 5 (excellent improvement) | 0 Participants |