A Study to Investigate the Effect of CYP3A Inhibition on the Pharmacokinetics of RO7017773 in Healthy Participants

• Sponsor: Hoffmann-La Roche (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03774576
• Collaborator: (none)
• Enrollment: 14
• Location: 1
• Arms: 2
• Actual Duration (Months): 2.9
• Patients Per Site Per Month: 4.9

Study Details

Study Description

Brief Summary

The purpose of this study is to investigate the effect of multiple oral doses of itraconazole on the pharmacokinetics of RO7017773 in healthy volunteers.

Condition or Disease	Intervention/Treatment	Phase
Healthy Volunteers	Drug: RO7017773; Drug: Itraconazole	Phase 1

Study Design

• Study Type: Interventional
• Actual Enrollment: 14 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Non-Randomized, Open Label, One Sequence, Two-Period Cross-Over Study to Investigate the Effect of CYP3A Inhibition on the Pharmacokinetics of RO7017773 in Healthy Participants
• Actual Study Start Date: Dec 17, 2018
• Actual Primary Completion Date: Mar 14, 2019
• Actual Study Completion Date: Mar 14, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: RO7017773 Single dose of RO7017773	Drug: RO7017773; Single doses of RO7017773
Experimental: RO7017773 and Itraconazole Single dose of RO7017773 and multiple doses of itraconazole	Drug: RO7017773; Single doses of RO7017773; Drug: Itraconazole; Multiple doses of Itraconazole; Other Names: Sporanox

Outcome Measures

Primary Outcome Measures

1. Maximum Concentration (Cmax) of RO7017773 in Plasma [Period 1 (RO7017773) and Period 2 (RO7017773 + Itraconazole)]

Secondary Outcome Measures

1. Percentage of Participants With Adverse Events (AEs) [12 weeks]

2. Change in Suicide Risk as Assessed Using the Columbia Suicide Severity Rating Scale (C-SSRS) [From screening visit through Period 2 Day 11]

   The C-SSRS is an assessment tool to evaluate suicidal ideation and behavior. Categories have binary responses (yes/no) and include: Wish to be Dead; Non-specific Active Suicidal Thoughts; Active Suicidal Ideation with Any Methods (Not Plan) without Intent to Act; Active Suicidal Ideation with Some Intent to Act, without Specific Plan; Active Suicidal Ideation with Specific Plan and Intent, Preparatory Acts and Behavior; Aborted Attempt; Interrupted Attempt; Actual Attempt (non-fatal); Completed Suicide. Suicidal ideation or behavior is indicated by a "yes" answer to any of the listed categories. A score of 0 is assigned if no suicide risk is present.

3. Cmax of Itraconazole in Plasma [Period 2]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 55 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria

• Healthy (absence of evidence of any active or chronic disease following a detailed medical and surgical history, a complete physical examination including vital signs, 12-lead ECG, hematology, blood chemistry, serology and urinalysis) as judged by the Investigator.

• Male and women of non-childbearing potential (WONCBP)

Exclusion Criteria

• History of convulsions (other than benign febrile convulsions of childhood) including epilepsy, or personal history of significant cerebral trauma or central nervous system (CNS) infections (e.g., meningitis)

• History of clinically significant hypersensitivity or allergic reactions

• Abnormal blood pressure

• Abnormal pulse rate

• History or presence of clinically significant ECG abnormalities before study drug administration or cardiovascular disease

• Current or chronic history of liver disease, or known hepatic or biliary abnormalities

• Positive test for drugs of abuse or alcohol

• Evidence of human immunodeficiency virus (HIV) infection

• Presence of hepatitis B surface antigen (HBsAg) or positive HCV antibody test result at screening or within 3 months prior to starting study treatment

• Participants who regularly smoke more than 5 cigarettes daily or the equivalent and are unable or unwilling not to smoke during the in-house period

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	BIOTRIAL	Rennes		France	35042

Sponsors and Collaborators

• Hoffmann-La Roche

Investigators

• Study Director: Clinical Trials, Hoffmann-La Roche

Study Documents (Full-Text)

• Study Protocol - Nov 14, 2018
• Statistical Analysis Plan - Apr 23, 2019

More Information

Publications

None provided.

• Responsible Party: Hoffmann-La Roche
• ClinicalTrials.gov Identifier: NCT03774576
• Other Study ID Numbers: BP40822; 2018-002889-40
• First Posted: Dec 13, 2018
• Last Update Posted: May 7, 2020
• Last Verified: Apr 1, 2020

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Itraconazole

Study Results

Participant Flow

Recruitment Details	Healthy male and female participants between 18 and 55 years old. Female participants were women of non-childbearing potential (WONCBP).

Arm/Group Title	RO7017773 Alone, Then RO7017773 + Itraconazole
Arm/Group Description	In Period 1, participants received a single dose of RO7017773 alone in a fed state. In Period 2, participants received a single dose of RO7017773 after repeated doses of itraconazole in a fed state.
Period Title: Period 1
STARTED	14
COMPLETED	14
NOT COMPLETED	0
Period Title: Period 1
STARTED	14
COMPLETED	13
NOT COMPLETED	1

Baseline Characteristics

Arm/Group Title	RO7017773 Alone, Then RO7017773 + Itraconazole
Arm/Group Description	In Period 1, participants received a single dose of RO7017773 alone in a fed state. In Period 2, participants received a single dose of RO7017773 after repeated doses of itraconazole in a fed state.
Overall Participants	14
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	44.1 (10.7)
Sex: Female, Male (Count of Participants)
Female	3 21.4%
Male	11 78.6%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%
Not Hispanic or Latino	14 100%
Unknown or Not Reported	0 0%

Outcome Measures

1. Primary Outcome

Title	Maximum Concentration (Cmax) of RO7017773 in Plasma
Time Frame	Period 1 (RO7017773) and Period 2 (RO7017773 + Itraconazole)

Outcome Measure Data

Analysis Population Description

The pharmacokinetic set (PKS) included all participants who received at least one dose of study treatment and who had data from at least one post-dose sample. This outcome measure is specific to the reported arms.

Arm/Group Title	RO7017773 Alone	RO7017773 + Itraconazole
Arm/Group Description	In Period 1, participants received a single dose of RO7017773 alone in a fed state.	In Period 2, participants received a single dose of RO7017773 after repeated doses of itraconazole in a fed state.
Measure Participants	13	13
Geometric Mean (Geometric Coefficient of Variation) [ng/mL]	458 (32.1)	516 (22.7)

2. Secondary Outcome

Title	Percentage of Participants With Adverse Events (AEs)
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

The safety set (SS) included all participants who received at least one dose of study treatment and included any participant(s) that were withdrawn from the study.

Arm/Group Title	RO7017773 Alone	Itraconazole Alone	RO7017773 + Itraconazole
Arm/Group Description	In Period 1, participants received a single dose of RO7017773 alone in a fed state.	In Period 2, participants received a single dose of RO7017773 after repeated doses of itraconazole in a fed state.	In Period 2, participants received a single dose of RO7017773 after repeated doses of itraconazole in a fed state.
Measure Participants	14	14	13
Number [Percentage of Participants]	57.1 407.9%	14.3 NaN	53.8 NaN

3. Secondary Outcome

Title	Change in Suicide Risk as Assessed Using the Columbia Suicide Severity Rating Scale (C-SSRS)
Description	The C-SSRS is an assessment tool to evaluate suicidal ideation and behavior. Categories have binary responses (yes/no) and include: Wish to be Dead; Non-specific Active Suicidal Thoughts; Active Suicidal Ideation with Any Methods (Not Plan) without Intent to Act; Active Suicidal Ideation with Some Intent to Act, without Specific Plan; Active Suicidal Ideation with Specific Plan and Intent, Preparatory Acts and Behavior; Aborted Attempt; Interrupted Attempt; Actual Attempt (non-fatal); Completed Suicide. Suicidal ideation or behavior is indicated by a "yes" answer to any of the listed categories. A score of 0 is assigned if no suicide risk is present.
Time Frame	From screening visit through Period 2 Day 11

Outcome Measure Data

Analysis Population Description

The included set (IS) contained all study participants.

Arm/Group Title	RO7017773 Alone	RO7017773 + Itraconazole
Arm/Group Description	In Period 1, participants received a single dose of RO7017773 alone in a fed state.	In Period 2, participants received a single dose of RO7017773 after repeated doses of itraconazole in a fed state.
Measure Participants	14	13
Screening	0 (0)	0 (0)
Period 2 Day 11	0 (0)	0 (0)

4. Secondary Outcome

Title	Cmax of Itraconazole in Plasma
Time Frame	Period 2

Outcome Measure Data

Analysis Population Description

The pharmacokinetic set (PKS) included all participants who received at least one dose of study treatment and who had data from at least one post-dose sample. This outcome measure is specific to the reported arm.

Arm/Group Title	RO7017773 Alone
Arm/Group Description	In Period 1, participants received a single dose of RO7017773 alone in a fed state.
Measure Participants	13
Geometric Mean (Geometric Coefficient of Variation) [ng/mL]	724 (43.2)

Adverse Events

Time Frame	12 weeks
Arm/Group Title	RO7017773 Alone		Itraconazole Alone		RO7017773 + Itraconazole
Arm/Group Description	In Period 1, participants received a single dose of RO7017773 alone in a fed state.		In Period 2, participants received a single dose of RO7017773 after repeated doses of itraconazole in a fed state.		In Period 2, participants received a single dose of RO7017773 after repeated doses of itraconazole in a fed state.
All Cause Mortality
	RO7017773 Alone		Itraconazole Alone		RO7017773 + Itraconazole
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/14 (0%)		0/14 (0%)		0/13 (0%)
Serious Adverse Events
	RO7017773 Alone		Itraconazole Alone		RO7017773 + Itraconazole
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/14 (0%)		0/14 (0%)		0/13 (0%)
Other (Not Including Serious) Adverse Events
	RO7017773 Alone		Itraconazole Alone		RO7017773 + Itraconazole
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	8/14 (57.1%)		2/14 (14.3%)		7/13 (53.8%)
Ear and labyrinth disorders
Tinnitus	0/14 (0%)	0	0/14 (0%)	0	1/13 (7.7%)	1
Gastrointestinal disorders
Diarrhoea	1/14 (7.1%)	1	0/14 (0%)	0	1/13 (7.7%)	1
Abdominal pain	0/14 (0%)	0	0/14 (0%)	0	1/13 (7.7%)	1
Faeces hard	0/14 (0%)	0	1/14 (7.1%)	1	0/13 (0%)	0
Flatulence	0/14 (0%)	0	0/14 (0%)	0	1/13 (7.7%)	1
General disorders
Chest pain	1/14 (7.1%)	1	0/14 (0%)	0	0/13 (0%)	0
Infections and infestations
Nasopharyngitis	3/14 (21.4%)	3	0/14 (0%)	0	0/13 (0%)	0
Bronchitis	1/14 (7.1%)	1	0/14 (0%)	0	0/13 (0%)	0
Musculoskeletal and connective tissue disorders
Back pain	2/14 (14.3%)	2	0/14 (0%)	0	0/13 (0%)	0
Arthralgia	0/14 (0%)	0	0/14 (0%)	0	1/13 (7.7%)	1
Nervous system disorders
Somnolence	1/14 (7.1%)	1	0/14 (0%)	0	4/13 (30.8%)	4
Dizziness	0/14 (0%)	0	0/14 (0%)	0	1/13 (7.7%)	1
Headache	1/14 (7.1%)	1	0/14 (0%)	0	0/13 (0%)	0
Skin and subcutaneous tissue disorders
Urticaria	0/14 (0%)	0	1/14 (7.1%)	1	0/13 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.