A Study to Assess the Clinical Effects of Navarixin in Participants With Psoriasis (MK-7123-009)

A Study to Assess the Clinical Effects of SCH 527123 in Psoriasis

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.

Study Overview

• Status: Completed
• Conditions: Psoriasis
• Intervention / Treatment: Drug: Navarixin 10 mg; Other: Placebo

• Study Type: Interventional
• Enrollment (Actual): 31
• Phase: Phase 2

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Navarixin; Navarixin 30 mg administered orally once daily for 28 days.	Drug: Navarixin 10 mg; Navarixin capsules orally, once daily for 28 days.
Placebo Comparator: Placebo; Matching placebo to Navarixin administered orally once daily for 28 days.	Other: Placebo; Matching placebo capsules to Navarixin orally, once daily for 28 days.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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).	Baseline and Day 29

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Day 29
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.	Day 28
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.	Day 28
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.	Day 28
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.	Day 28

Collaborators and Investigators

• Sponsor: Merck Sharp & Dohme LLC

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2007
• Primary Completion (Actual): October 1, 2007
• Study Completion (Actual): October 1, 2007

Study Registration Dates

• First Submitted: May 22, 2008
• First Submitted That Met QC Criteria: May 22, 2008
• First Posted (Estimate): May 26, 2008

Study Record Updates

• Last Update Posted (Actual): February 5, 2019
• Last Update Submitted That Met QC Criteria: January 17, 2019
• Last Verified: January 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Skin Diseases, Papulosquamous; Psoriasis
• Other Study ID Numbers: P04481 (Other Identifier: Merck Protocol Number); 2006-006601-83 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf

Study Data/Documents

1. CSR Synopsis