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

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ClinicalTrials.gov Identifier: NCT02607774
Recruitment Status : Completed
First Posted : November 18, 2015
Last Update Posted : April 2, 2019
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Moderate to Severe Plaque Psoriasis Drug: Midazolam Drug: AIN457 Phase 1

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.


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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 25 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Basic Science
Official Title: 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
Actual Study Start Date : December 17, 2015
Actual Primary Completion Date : December 20, 2016
Actual Study Completion Date : December 20, 2016

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Psoriasis

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 Name: Secukinumab




Primary Outcome Measures :
  1. Cmax (maximum plasma) concentration [ Time Frame: Days -7, 8 and 36 ]
  2. AUC0-12 (area under the plasma concentration-time curve from time zero to time 12 hours ) [ Time Frame: Days -7, 8 and 36 ]
  3. AUClast (area under the plasma concentration-time curve from time zero to the time of the last quantifiable concentration) [ Time Frame: Days -7, 8 and 36 ]
  4. AUCinf (area under the plasma concentration-time curve from time zero to infinity) [ Time Frame: Days -7, 8 and 36 ]

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


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02607774


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

Additional Information:
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Responsible Party: Novartis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT02607774     History of Changes
Other Study ID Numbers: CAIN457A2110
First Posted: November 18, 2015    Key Record Dates
Last Update Posted: April 2, 2019
Last Verified: March 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Novartis ( Novartis Pharmaceuticals ):
Plaque psoriasis
disease-drug-drug-interaction
midazolam
secukinumab
Additional relevant MeSH terms:
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Psoriasis
Skin Diseases, Papulosquamous
Skin Diseases
Midazolam
Antibodies, Monoclonal
Adjuvants, Anesthesia
Hypnotics and Sedatives
Central Nervous System Depressants
Physiological Effects of Drugs
Anti-Anxiety Agents
Tranquilizing Agents
Psychotropic Drugs
Anesthetics, Intravenous
Anesthetics, General
Anesthetics
GABA Modulators
GABA Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Immunologic Factors