Investigate Effect of Secukinumab on the PK of Midazolam in Patients With Mod to Sev Plaque Psoriasis

An Open-label, Single Sequence Crossover, Study Investigating the Influence of Secukinumab Treatment on the Pharmacokinetics of Midazolam as a CYP3A4 Substrate in Patients With Moderate to Severe Plaque Psoriasis

To determine whether secukinumab can alter the activity of cytochrome P450 (CYP) 3A4 using midazolam as probe substrate in patients with moderate-to-severe plaque psoriasis.

Study Overview

• Status: Completed
• Conditions: Moderate to Severe Plaque Psoriasis
• Intervention / Treatment: Drug: Midazolam; Drug: AIN457

Detailed Description

This will be an open-label, confirmatory study investigating potential disease-drug-drug interaction of secukinumab and midazolam in male and female patients with moderate-to-severe plaque psoriasis. A total of approximately 25 patients are required to obtain at least 20 completers in the study Patients who meet the eligibility criteria at screening, will have a baseline assessment day (within 1 week prior to the start of secukinumab) during which a full midazolam PK profile after a single oral dose of 5 mg will be assessed by collecting blood over the 12 hour postdose period.

On Day 1 (Week 0), Day 8 (Week 1), Day 15 (Week 2), Day 22 (Week 3) and Day 29 (Week 4) patients will receive 300 mg s.c. secukinumab (2 injections of 150 mg s.c.). On Day 8 and on Day 36 (Week 5), patients will receive additional single doses of 5 mg oral midazolam (total of 3 single doses). The midazolam PK profile will be assessed over the 12 hour postdose period.

On those days when midazolam PK profiles are assessed, samples will be collected and analyzed for circulating IL-6, inflammatory panel (collected at screening, baseline and pre-dose Day 1 only), total IL-17A (after following initiation of secukinumab treatment), hsCRP and for 4-beta-hydroxycholesterol (exploratory endogenous phenotyping marker of CYP3A activity).

There will be an extended treatment period during which patients will receive secukinumab 300 mg s.c. at Weeks 8, 12, 16, 20 and 24.

Then there will be a follow-up period of 12 weeks following the last dose administered at Week 24. Visits will be at Weeks 28, 32 and 36.

• Study Type: Interventional
• Enrollment (Actual): 25
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35205
      • Novartis Investigative Site
  • Arizona
    • Phoenix, Arizona, United States, 85032
      • Novartis Investigative Site
  • Arkansas
    • Hot Springs, Arkansas, United States, 71913
      • Novartis Investigative Site
  • New Jersey
    • Fair Lawn, New Jersey, United States, 07410
      • Novartis Investigative Site
    • Verona, New Jersey, United States, 07044
      • Novartis Investigative Site
  • Texas
    • Dallas, Texas, United States, 75230
      • Novartis Investigative Site
    • Webster, Texas, United States, 77004
      • Novartis Investigative Site
  • Virginia
    • Norfolk, Virginia, United States, 23507
      • Novartis Investigative Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Moderate to severe plaque psoriasis as defined at baseline by: PASI score of 12 or greater and IGA mod 2011 score of 3 or greater (based on a scale of 0 - 4) and Body Surface Area (BSA) affected by plaque-type psoriasis of 10% or greater.
• Chronic plaque-type psoriasis considered inadequately controlled by: topical treatment and/or; phototherapy and/or previous systemic therapy
• Men or women at least 18 years of age or older at time of screening.

Exclusion Criteria:

• Forms of psoriasis other than chronic plaque-type
• Pregnant or nursing (lactating) women,
• History of an ongoing, chronic or recurrent infectious disease, or evidence of tuberculosis infection.
• Subjects with known history of hypersensitivity to midazolam

Study Plan

How is the study designed?

Design Details

• Primary Purpose: BASIC_SCIENCE
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Secukinumab; Secukinumab over 24 weeks	Drug: Midazolam; midazolam administered to all patients Days -7, 1 and 35.; Drug: AIN457; secukinumab administered at Weeks 0, 1, 2, 3, 4, 8, 12, 16, 20 and 24; Other Names: Secukinumab

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Cmax (maximum plasma) concentration	Days -7, 8 and 36
AUC0-12 (area under the plasma concentration-time curve from time zero to time 12 hours )	Days -7, 8 and 36
AUClast (area under the plasma concentration-time curve from time zero to the time of the last quantifiable concentration)	Days -7, 8 and 36
AUCinf (area under the plasma concentration-time curve from time zero to infinity)	Days -7, 8 and 36

Secondary Outcome Measures

Outcome Measure	Time Frame
safety and tolerability (including; Blood pressure,Pulse Rate,AEs/SAEs, Blood chemistry, Hematology, ECGs and physical exam	Throughout the entire trial; beginning at screening through Day 253 (end of trial)

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Publications and helpful links

Helpful Links

• A Plain Language Trial Summary is available on novartisclinicaltrials.com
• Results for CAIN457A2110 can be found on the Novartis Clinical Trial Results Website

Study record dates

Study Major Dates

• Study Start (ACTUAL): December 17, 2015
• Primary Completion (ACTUAL): December 20, 2016
• Study Completion (ACTUAL): December 20, 2016

Study Registration Dates

• First Submitted: November 3, 2015
• First Submitted That Met QC Criteria: November 16, 2015
• First Posted (ESTIMATE): November 18, 2015

Study Record Updates

• Last Update Posted (ACTUAL): December 11, 2020
• Last Update Submitted That Met QC Criteria: December 9, 2020
• Last Verified: March 1, 2019

More Information

Terms related to this study

• Keywords: midazolam; Plaque psoriasis; secukinumab; disease-drug-drug-interaction
• Additional Relevant MeSH Terms: Skin Diseases; Skin Diseases, Papulosquamous; Psoriasis; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Tranquilizing Agents; Psychotropic Drugs; Hypnotics and Sedatives; Adjuvants, Anesthesia; Anti-Anxiety Agents; GABA Modulators; GABA Agents; Midazolam
• Other Study ID Numbers: CAIN457A2110

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No