Brodalumab Drug-Drug Interaction (DDI) and Intensive Pharmacodynamic (PK) Study in Psoriasis Subjects

• Sponsor: Bausch Health Americas, Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01937260
• Collaborator: (none)
• Enrollment: 31
• Locations: 10
• Arms: 2
• Duration (Months): 15
• Patients Per Site: 3.1
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

This is a phase 1, multi-center, open-label, drug-drug interaction (DDI) and PK study in subjects with moderate to severe plaque psoriasis. It is designed to evaluate the effect of brodalumab on midazolam PK in addition to assessing single dose PK of brodalumab in subjects with moderate to severe plaque psoriasis.

Condition or Disease	Intervention/Treatment	Phase
Psoriasis	Drug: Brodalumab	Phase 1

Detailed Description

Approximately 30 subjects will be enrolled into two groups. Group 1 consists of 20 subjects and will receive 2 oral doses of midazolam and a single subcutaneous (SC) dose of brodalumab. Group 2 consists of 10 subjects and will receive a single SC dose of brodalumab.

Study Design

• Study Type: Interventional
• Actual Enrollment: 31 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Other
• Official Title: An Open-label Study to Evaluate the Effect of Brodalumab on the Pharmacokinetics of Midazolam and Assess Single-Dose Brodalumab Pharmacokinetics in Subjects With Moderate to Severe Plaque Psoriasis
• Study Start Date: Sep 1, 2013
• Actual Primary Completion Date: Jul 1, 2014
• Actual Study Completion Date: Dec 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Brodalumab 140mg SC open label, all subjects receive brodulamab	Drug: Brodalumab; Group 1 consists of 20 subjects and will receive 2 oral doses of midazolam and a single SC dose of brodalumab. Group 2 consists of 10 subjects and will receive a single SC dose of brodalumab.; Other Names: AMG 827
Experimental: Midazolam (MDZ) 2mg oral, Brodalumab 210mg SC MDZ 2mg oral (Day 1 and Day 9), Brodalumab 210mg SC (Day 2)	Drug: Brodalumab; Group 1 consists of 20 subjects and will receive 2 oral doses of midazolam and a single SC dose of brodalumab. Group 2 consists of 10 subjects and will receive a single SC dose of brodalumab.; Other Names: AMG 827

Outcome Measures

Primary Outcome Measures

1. The Maximum Observed Concentration of Midazolam After a Single Dose of Brodalumab [Day 1 to day 9]

   Midazolam pharmacokinetic parameter estimates after single oral dose of Midazolam 2 mg on Day 1 and Day 9 and a single administration of Brodalumab 210 mg on Day 2 with PK sampling collected on Day 30

2. The Area Under Drug Concentration Time Curve From Zero to Infinity (AUCinf) [Day 1 to Day 9]

   Midazolam pharmacokinetic parameter estimates after single oral dose of Midazolam 2 mg on Day 1 and Day 9 and a single administration of Brodalumab 210 mg on Day 2 with PK sampling collected on day 30

3. The Area Under the Drug-concentration Curve of Midazolam After a Single Dose of Brodalumab From Zero Tot he Last Time of Quantifiable Concentration [Day 1 to Day 9]

   Midazolam pharmacokinetic parameter estimates after single oral dose of Midazolam 2 mg on Day 1 and Day 9 and a single administration of Brodalumab 210 mg on Day 2

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 75 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Subject has had stable moderate to severe plaque psoriasis for at least 6 months

• body mass index (BMI) between ≥ 18.0 and ≤ 38.0 kg/m2

• body weight between ≥ 50 and ≤ 130 kg

• no known history of active tuberculosis

Exclusion Criteria:

• Female subjects who are lactating/breastfeeding

• History or evidence of clinically significant disorder, condition or disease that, in the opinion of the investigator or Amgen physician would pose a risk to subject safety or interfere with the study evaluation, procedures or completion.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Research Site	Anaheim	California	United States	92801
2	Research Site	Irvine	California	United States	92697
3	Research Site	Ocala	Florida	United States	34471
4	Research Site	Austin	Texas	United States	78759
5	Research Site	Dallas	Texas	United States	75231
6	Research Site	Herston	Queensland	Australia	4006
7	Research Site	Adelaide	South Australia	Australia	5000
8	Research Site	Prahran	Victoria	Australia	3181
9	Research Site	Christchurch		New Zealand	8011
10	Research Site	Grafton, Auckland		New Zealand	1010

Sponsors and Collaborators

• Bausch Health Americas, Inc.

Investigators

• Study Director: MD, Amgen

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• AmgenTrials clinical trials website

Publications

None provided.

• Responsible Party: Bausch Health Americas, Inc.
• ClinicalTrials.gov Identifier: NCT01937260
• Other Study ID Numbers: 20110184
• First Posted: Sep 9, 2013
• Last Update Posted: Apr 10, 2017
• Last Verified: Apr 1, 2017

• Additional relevant MeSH terms: Psoriasis; Brodalumab

Study Results

Participant Flow

Arm/Group Title	Cohort 1	Cohort 2
Arm/Group Description	Midazolam (MDZ) 2mg Oral (Day 1 and Day 9) Brodalumab 210 mg SC (Day 2)	Brodalumab 140 mg SC (Day 1)
Period Title: Overall Study
STARTED	21	10
COMPLETED	20	10
NOT COMPLETED	1	0

Baseline Characteristics

Arm/Group Title	Cohort 1	Cohort 2	Total
Arm/Group Description	Midazolam (MDZ) 2mg oral (Day 1 and Day 9) Brodalumab 210mg SC (Day 2)	Brodalumab 140mg SC (Day1)	Total of all reporting groups
Overall Participants	21	10	31
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	21 100%	10 100%	31 100%
>=65 years	0 0%	0 0%	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	41.2 (10.9)	46.8 (15.6)	43 (12.6)
Sex: Female, Male (Count of Participants)
Female	15 71.4%	9 90%	24 77.4%
Male	6 28.6%	1 10%	7 22.6%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	1 4.8%	2 20%	3 9.7%
Native Hawaiian or Other Pacific Islander	1 4.8%	0 0%	1 3.2%
Black or African American	1 4.8%	0 0%	1 3.2%
White	16 76.2%	8 80%	24 77.4%
More than one race	2 9.5%	0 0%	2 6.5%
Unknown or Not Reported	0 0%	0 0%	0 0%

Outcome Measures

1. Primary Outcome

Title	The Maximum Observed Concentration of Midazolam After a Single Dose of Brodalumab
Description	Midazolam pharmacokinetic parameter estimates after single oral dose of Midazolam 2 mg on Day 1 and Day 9 and a single administration of Brodalumab 210 mg on Day 2 with PK sampling collected on Day 30
Time Frame	Day 1 to day 9

Outcome Measure Data

Analysis Population Description

Analysis population is now 20 subjects after 1 subject was discontinued by sponsor decision

Arm/Group Title	Cohort 1
Arm/Group Description	Midazolam (MDZ) 2mg oral (Day 1 and Day 9) Brodalumab 210mg SC (Day 2)
Measure Participants	20
Mean (Standard Deviation) [nanograms per milliliter]	11.5 (4.59)

2. Primary Outcome

Title	The Area Under Drug Concentration Time Curve From Zero to Infinity (AUCinf)
Description	Midazolam pharmacokinetic parameter estimates after single oral dose of Midazolam 2 mg on Day 1 and Day 9 and a single administration of Brodalumab 210 mg on Day 2 with PK sampling collected on day 30
Time Frame	Day 1 to Day 9

Outcome Measure Data

Analysis Population Description

20 subjects analyzed after the discontinuation of 1 subject by sponsor decision

Arm/Group Title	Cohort 1
Arm/Group Description	Midazolam (MDZ) 2mg oral (Day 1 and Day 9)Brodalumab 210mg SC (Day 2)
Measure Participants	20
Mean (Standard Deviation) [hr*ng/mL]	41.5 (22.1)

3. Primary Outcome

Title	The Area Under the Drug-concentration Curve of Midazolam After a Single Dose of Brodalumab From Zero Tot he Last Time of Quantifiable Concentration
Description	Midazolam pharmacokinetic parameter estimates after single oral dose of Midazolam 2 mg on Day 1 and Day 9 and a single administration of Brodalumab 210 mg on Day 2
Time Frame	Day 1 to Day 9

Outcome Measure Data

Analysis Population Description

20 subjects are now analyzed after the discontinuation of 1 subject by sponsor decision

Arm/Group Title	Cohort 1
Arm/Group Description	Midazolam (MDZ) 2mg oral (Day 1 and Day 9) Brodalumab 210mg SC (Day 2)
Measure Participants	20
Mean (Standard Deviation) [hr*ng/mL]	39 (19.2)

Adverse Events

Arm/Group Title	Cohort 1		Cohort 2
Arm/Group Description	Midazolam (MDZ) 2mg oral (Day 1 and Day 9) Brodalumab 210mg SC (Day 2)		Brodalumab 140mg SC (Day1)
All Cause Mortality
	Cohort 1		Cohort 2
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Cohort 1		Cohort 2
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/20 (0%)		0/10 (0%)
Other (Not Including Serious) Adverse Events
	Cohort 1		Cohort 2
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	13/20 (65%)		5/10 (50%)
Blood and lymphatic system disorders
Anaemia	1/20 (5%)		0/10 (0%)
Cardiac disorders
Palpatations	1/20 (5%)		0/10 (0%)
Ear and labyrinth disorders
Ear Congestion	1/20 (5%)		0/10 (0%)
Gastrointestinal disorders
Crohn's Disease	0/20 (0%)		1/10 (10%)
Abdominal Discomfort	0/20 (0%)		1/10 (10%)
Abdominal Pain	0/20 (0%)		1/10 (10%)
General disorders
Injection Site reaction	0/20 (0%)		1/10 (10%)
Pyrexia	0/20 (0%)		1/10 (10%)
Catheter Site Pain	1/20 (5%)		0/10 (0%)
Fatigue	1/20 (5%)		0/10 (0%)
Infected Bites	1/20 (5%)		0/10 (0%)
Upper Respiratory Tract Infection	1/20 (5%)		0/10 (0%)
Musculoskeletal and connective tissue disorders
Muscle Strain	0/20 (0%)		1/10 (10%)
Nervous system disorders
Dysgeusia	2/20 (10%)		0/10 (0%)
Somnolence	2/20 (10%)		0/10 (0%)
presyncope	1/20 (5%)		0/10 (0%)
headache	1/20 (5%)		0/10 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.