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

Moderate to Severe Plaque Psoriasis Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02607774
• Other study ID #: CAIN457A2110
• Status: Completed
• Phase: Phase 1
• Start date: December 17, 2015
• Est. completion date: December 20, 2016

Study information

• Verified date: March 2019
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 25
• Est. completion date: December 20, 2016
• Est. primary completion date: December 20, 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Moderate to Severe Plaque Psoriasis
• Psoriasis

Intervention

Drug:
• Midazolam
midazolam administered to all patients Days -7, 1 and 35.
• AIN457
secukinumab administered at Weeks 0, 1, 2, 3, 4, 8, 12, 16, 20 and 24

Locations

Country	Name	City	State
United States	Novartis Investigative Site	Birmingham	Alabama
United States	Novartis Investigative Site	Dallas	Texas
United States	Novartis Investigative Site	Fair Lawn	New Jersey
United States	Novartis Investigative Site	Hot Springs	Arkansas
United States	Novartis Investigative Site	Norfolk	Virginia
United States	Novartis Investigative Site	Phoenix	Arizona
United States	Novartis Investigative Site	Verona	New Jersey
United States	Novartis Investigative Site	Webster	Texas

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Cmax (maximum plasma) concentration		Days -7, 8 and 36
Primary	AUC0-12 (area under the plasma concentration-time curve from time zero to time 12 hours )		Days -7, 8 and 36
Primary	AUClast (area under the plasma concentration-time curve from time zero to the time of the last quantifiable concentration)		Days -7, 8 and 36
Primary	AUCinf (area under the plasma concentration-time curve from time zero to infinity)		Days -7, 8 and 36
Secondary	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)

External Links

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