This Study Tests the Effect of Risankizumab on the Metabolism in the Liver of Five Additional Drugs to Study Possible Drug Interactions in Patients With Psoriasis With or Without Psoriatic Arthritis

• Register: ClinicalTrials.gov
• Last refreshed on: 16 December 2017
• Main ID: NCT02772601
• Date of registration: 12/05/2016
• Prospective Registration: Yes
• Primary sponsor: AbbVie
• Public title: This Study Tests the Effect of Risankizumab on the Metabolism in the Liver of Five Additional Drugs to Study Possible Drug Interactions in Patients With Psoriasis With or Without Psoriatic Arthritis
• Scientific title: The Effect of Multiple Subcutaneous Doses of Risankizumab on the Single Dose Pharmacokinetics of Cytochrome P450 Substrates (Caffeine, Warfarin, Omeprazole, Metoprolol and Midazolam) Administered Orally in an Open-label, One-sequence Trial in Patients With Plaque Psoriasis With or Without Concomitant Psoriatic Arthritis
• Date of first enrolment: September 15, 2016
• Target sample size: 21
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT02772601
• Study type: Interventional
• Study design: Intervention model: Single Group Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 1

Countries of recruitment

Germany

Contacts

• Name: Lawrence Mcnamee
• Affiliation: AbbVie

Key inclusion & exclusion criteria

Inclusion criteria:

- Signed and dated written informed consent in accordance with GCP (Good Clinical
Practice) and local legislation prior to admission to the trial and prior to any trial
related procedure.

- Age 18 years to 75 years at screening

- Body mass index of 18.5 to 40.0 kg/m2 and within the weight range of 50 to 148 kg

- Male or female patients.

- If female, subject must be either postmenopausal, defined as:

- Age > 55 years with no menses for 12 or more months without an alternative
medical cause.

- Age < 55 years with no menses for 12 or more months without an alternative
medical cause AND an FSH level > 40 IU/L.

OR

- Permanently surgically sterile (bilateral oophorectomy, bilateral salpingectomy or
hysterectomy).

- Females must have negative results for pregnancy tests performed:

- at Screening on a urine sample obtained within 30 days prior to initial study
drug administration, and

- prior to initial dosing on a serum sample obtained at the start of confinement

- Women of Childbearing Potential (WOCBP) must practice at least one of the following
methods of birth control, on Study Day 1 (or earlier) through at least 140 days after
the last dose of study drug.

- Combined (estrogen and progestogen containing) hormonal contraception (oral,
intravaginal, transdermal) associated with the inhibition of ovulation, initiated
at least 1 month prior to Study Day 1.

- Progestogen-only hormonal contraception (oral, injectable, implantable)
associated with inhibition of ovulation, initiated at least 1 month prior to
Study Day 1.

- Bilateral tubal occlusion/ligation.

- Vasectomized partner(s), provided the vasectomized partner has received medical
assessment of the surgical success and is the sole sexual partner of the WOCBP
trial participant.

- Intrauterine device (IUD).

- Intrauterine hormone-releasing system (IUS).

- True abstinence: Refraining from heterosexual intercourse-when this is in line
with the preferred and usual lifestyle of the subject. (Note: Periodic abstinence
[e.g., calendar, ovulation, symptothermal, post-ovulation methods] and withdrawal
are not acceptable).

- Further inclusion criteria apply.

Exclusion criteria:

- Patients with

- non-plaque forms of psoriasis (including guttate, erythrodermic, or pustular)

- current drug-induced psoriasis (including an exacerbation of psoriasis from beta
blockers, calcium channel blockers, or lithium)

- active ongoing inflammatory diseases other than psoriasis that might confound
trial evaluations according to investigator's judgment

- Participation in another trial with an investigational drug or device within 4 weeks
or 5 half-lives (whichever is greater) prior to screening. Observational study is
permitted.

- Patients who must or wish to continue the intake of restricted medications or any drug
considered likely to interfere with the safe conduct of the study, as assessed by the
investigator

- Major surgery performed within 12 weeks prior to screening or planned within 10 months
after screening (e.g. hip replacement, aneurysma removal, stomach ligation)

- Active systemic infections during the last 2 weeks (exception: common cold) prior to
screening

- Chronic or relevant acute infections including HIV (Human Immunodeficiency Virus),
viral hepatitis and (or) tuberculosis or evidence of tuberculosis infection as defined
by a positive QuantiFERON TB (tuberculosis) test within 2 months prior to or during
screening. Patients with a positive QuantiFERON TB test may participate in the study
if further work up including a chest X-ray (according to local practice/guidelines)
establishes conclusively that the patient has no evidence of active tuberculosis and
initiation of treatment during the conduct of this study is not needed. If presence of
latent tuberculosis is established, then treatment according to local country
guidelines must have been initiated and completed prior to study initiation.

- Active HBV (Hepatitis B Virus) and HCV (Hepatitis C Virus), defined as:

- HBV: hepatitis B surface antigen (HBs Ag) positive (+),HBcAb positive or detected
sensitivity on the HBV deoxyribonucleic acid (DNA) polymerase chain reaction
(PCR) qualitative test for Hepatitis B core antibody (HBc Ab);

- HCV: HCV ribonucleic acid (RNA) detectable in any subject with anti-HCV antibody
(HCV Ab).

- Positive screen for drugs of abuse, alcohol or cotinine at Screening.

- Use of known inhibitors or inducers of CYP1A2, 2C9, 2C19, 2D6 or 3A4, including
dietary supplements or herbal products containing St. John's wort (Hypericum
perforatum) or other known CYP inducers or inhibitors within 30 days or 5 half-lives,
whichever is greater prior to study CYP cocktail probe drug administration.

- Use of grapefruits, Seville oranges (sour or bitter oranges), starfruit and their
juices, quinine, tonic water, dietary/herbal supplements and inhibitors of
P-glycoprotein (P-gp), breast cancer resistance protein (BCRP) and organic
anion-transporting polypeptide 1B1/1B3 (OATP1B1/1B3) transporters within 14 days or 5
half-lives of the respective medication before CYP cocktail probe drug administration.

- Current smokers of nicotine containing products, including those who quit smoking less
than 30 days prior to CYP cocktail probe drug administration.

- Any documented active or suspected malignancy or history of malignancy within 5 years
prior to screening, except appropriately treated basal or squamous cell carcinoma of
the skin or in situ carcinoma of uterine cervix

- Plans for administration of live vaccines during the study period or within 6 weeks
prior to screening

- Further exclusion criteria apply.



Age minimum: 18 Years
Age maximum: 75 Years
Gender: All

Health Condition(s) or Problem(s) studied

Psoriasis

Intervention(s)

Drug: Caffeine

Drug: Metoprolol

Drug: Midazolam

Drug: Omeprazole

Drug: Risankizumab

Drug: Warfarin

Primary Outcome(s)

AUC0 - tz (area under the concentration-time curve) of midazolam without risankizumab in plasma over time interval from 0 to last quantifiable data point [Time Frame: Day 1-2]

Cmax (maximum measured concentration) of the analyte caffeine without risankizumab in plasma [Time Frame: Day 1]

Cmax (maximum measured concentration) of the analyte omeprazole with risankizumab in plasma [Time Frame: Day 98]

AUC0 - tz (area under the concentration-time curve) of midazolam with risankizumab in plasma over time interval from 0 to last quantifiable data point [Time Frame: Day 98 - 99]

AUC0 - tz (area under the concentration-time curve) of caffeine with risankizumab in plasma over time interval from 0 to last quantifiable data point [Time Frame: Day 98-101]

AUC0 - tz (area under the concentration-time curve) of caffeine without risankizumab in plasma over time interval from 0 to last quantifiable data point [Time Frame: Day 1-3]

AUC0 - tz (area under the concentration-time curve) of metoprolol without risankizumab in plasma over time interval from 0 to last quantifiable data point [Time Frame: Day 1-3]

Cmax (maximum measured concentration) of the analyte omeprazole without risankizumab in plasma [Time Frame: Day 1]

AUC0 - tz (area under the concentration-time curve) of omeprazole without risankizumab in plasma over time interval from 0 to last quantifiable data point [Time Frame: Day 1-2]

AUC0 - tz (area under the concentration-time curve) of warfarin with risankizumab in plasma over time interval from 0 to last quantifiable data point [Time Frame: Day 98 - 105]

Cmax (maximum measured concentration) of the analyte caffeine with risankizumab in plasma [Time Frame: Day 98]

AUC0 - tz (area under the concentration-time curve) of metoprolol with risankizumab in plasma over time interval from 0 to last quantifiable data point [Time Frame: Day 98 -100]

Cmax (maximum measured concentration) of the analyte metoprolol with risankizumab in plasma [Time Frame: Day 98]

AUC0 - tz (area under the concentration-time curve) of omeprazole with risankizumab in plasma over time interval from 0 to last quantifiable data point [Time Frame: Day 98 - 100]

Cmax (maximum measured concentration) of the analyte midazolam with risankizumab in plasma [Time Frame: Day 98]

AUC0 - tz (area under the concentration-time curve) of warfarin without risankizumab in plasma over time interval from 0 to last quantifiable data point [Time Frame: Day 1-8]

Cmax (maximum measured concentration) of the analyte warfarin with risankizumab in plasma [Time Frame: Day 98]

Cmax (maximum measured concentration) of the analyte midazolam without risankizumab in plasma [Time Frame: Day 1]

Cmax (maximum measured concentration) of the analyte warfarin without risankizumab in plasma [Time Frame: Day 1]

Cmax (maximum measured concentration) of the analyte metoprolol without risankizumab in plasma [Time Frame: Day 1]

Secondary ID(s)

M16-007

1311.36

2015-005523-31

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

Boehringer Ingelheim