A 2 Part Study to Assess the Relative Bioavailability of Tablet Formulation Compared to Capsule Formulation and the Effect of Food and Taste Assessment on the Tablet Formulation in Healthy Participants

• Sponsor: Hoffmann-La Roche (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03847987
• Collaborator: (none)
• Enrollment: 24
• Location: 1
• Arms: 2
• Actual Duration (Months): 1.3
• Patients Per Site Per Month: 17.8

Study Details

Study Description

Brief Summary

This is a two-part, open-label, healthy volunteer study. Part I will investigate the relative bioavailability of capsule and tablet formulations of RO7017773. Part II will explore how the taste of the tablet formulation is perceived with and without added sweetener/flavoring.

Condition or Disease	Intervention/Treatment	Phase
Healthy Volunteers	Drug: RO7017773 Phase I Capsule; Drug: RO7017773 Phase II Tablet Unflavored; Drug: RO7017773 Phase II Tablet Sweetened/Flavored	Phase 1

Study Design

• Study Type: Interventional
• Actual Enrollment: 24 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A 2 Part, Randomized, Open-Label, Single Dose, Crossover Study to Assess the Relative Bioavailability of Phase II Tablet Formulation Compared to the Current Phase I Capsule Formulation and the Effect of Food and Taste Assessment on the Phase II Tablet Formulation in Healthy Participants
• Actual Study Start Date: Mar 12, 2019
• Actual Primary Completion Date: Apr 22, 2019
• Actual Study Completion Date: Apr 22, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Part 1 Participants will receive 4 single oral doses of RO7017773 under either fed or fasted conditions, one of which will be a taste assessment. There will be a 7-10 day washout period between doses.	Drug: RO7017773 Phase I Capsule; Participants will receive 1 single oral dose of RO7017773 Phase I Capsule.; Drug: RO7017773 Phase II Tablet Unflavored; Participants will receive 3 single oral doses of unflavored RO7017773 Phase II tablet during Part 1, and 1 single oral dose of unflavored RO7017773 Phase II tablet during Part 2.
Experimental: Part 2 Participants will receive 2 single oral doses of RO7017773, either sweetened/flavored, or unflavored and dispersed in juice. There will be a 7-10 day washout period between doses.	Drug: RO7017773 Phase II Tablet Unflavored; Participants will receive 3 single oral doses of unflavored RO7017773 Phase II tablet during Part 1, and 1 single oral dose of unflavored RO7017773 Phase II tablet during Part 2.; Drug: RO7017773 Phase II Tablet Sweetened/Flavored; Participants will receive 1 single oral dose of sweetened/flavored RO7017773 Phase II tablet during Part 2.

Outcome Measures

Primary Outcome Measures

1. Maximum Observed Plasma Concentration (Cmax) of RO7017773 (Part 1) [Day 1 to Day 5]

2. Cmax of RO7017773 (Part 2) [Day 1 to Day 5]

3. Taste Assessment, as Measured by Taste Questionnaire (Part 2) [Day 1]

   Taste was assessed using a questionnaire that asking participants to rate the overall taste of study drug dispersed in various vehicles on a scale from 1-5, with 1=no taste, and 5=very intense taste.

Secondary Outcome Measures

1. Taste Assessment, as Measured by Taste Questionnaire (Part 1) [Day 1]

   Taste was assessed using a questionnaire that asking participants to rate the overall taste of study drug dispersed in various vehicles on a scale from 1-5, with 1=no taste, and 5=very intense taste.

2. Percentage of Participants With Adverse Events (AEs) [Baseline through end of study (approximately 6 weeks)]

Eligibility Criteria

Criteria

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

Inclusion Criteria

• Non-smoker for at least six months

• Healthy, as judged by the Investigator

• Women of non-childbearing potential (WONCBP) who are not pregnant or lactating

• Men must be willing to remain abstinent or agree to use contraceptive measures with partners who are women of childbearing potential (WOCBP), and must refrain from donating sperm, for at least 28 days after the last dose of study drug

Exclusion Criteria

• History or evidence of any medical condition potentially altering the absorption, metabolism or elimination of drugs

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

• A history of clinically significant hypersensitivity (e.g., drugs, excipients) or allergic reactions

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

• Have used or intend to use over-the-counter or prescription medication including herbal medications within 30 days prior to dosing

• Participation in an investigational drug or device study within 90 days prior to screening

• Human immunodeficiency virus (HIV) infection and/or positive human HIV antibodies

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	PRA Health Sciences	Salt Lake City	Utah	United States	84124

Sponsors and Collaborators

• Hoffmann-La Roche

Investigators

• Study Director: Clinical Trials, Hoffmann-La Roche

Study Documents (Full-Text)

• Study Protocol - Feb 28, 2019
• Statistical Analysis Plan - Apr 26, 2019

More Information

Publications

None provided.

• Responsible Party: Hoffmann-La Roche
• ClinicalTrials.gov Identifier: NCT03847987
• Other Study ID Numbers: BP40950
• First Posted: Feb 20, 2019
• Last Update Posted: May 28, 2020
• Last Verified: May 1, 2020

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Study Results

Participant Flow

Recruitment Details	Healthy male and female participants between ages 18-55 years, who were nonsmokers for at least 6 months.

Arm/Group Title	Part 1	Part 2
Arm/Group Description	Sixteen (16) total participants received each of the following treatments, with a 7-10 day washout period between treatments: Treatment A = A single oral dose of RO7017773 (capsule) swallowed whole under fasted conditions Treatment B = A single oral dose of RO7017773 (tablet) swallowed whole under fasted conditions Treatment C = A single oral dose of RO7017773 (tablet) swallowed whole under fed conditions Treatment D = A single oral dose of RO7017773 (tablet) dispersed in water under fasted conditions Treatment sequences were randomly assigned	Eight (8) total participants received each of the following treatments, with a 7-10 day washout period between treatments: Treatment A (taste assessment) = A single oral dose of RO7017773 (tablet) containing flavor/sweetener dispersed in water under fasted conditions Treatment B (taste assessment) = A single oral dose of RO7017773 (tablet) with no flavor/sweetener dispersed in apple juice under fasted conditions Treatment sequences were randomly assigned
Period Title: Overall Study
STARTED	16	8
COMPLETED	13	8
NOT COMPLETED	3	0

Baseline Characteristics

Arm/Group Title	Part 1	Part 2	Total
Arm/Group Description	Sixteen (16) total participants received each of the following treatments, with a 7-10 day washout period between treatments: Treatment A = A single oral dose of RO7017773 (capsule) swallowed whole under fasted conditions Treatment B = A single oral dose of RO7017773 (tablet) swallowed whole under fasted conditions Treatment C = A single oral dose of RO7017773 (tablet) swallowed whole under fed conditions Treatment D = A single oral dose of RO7017773 (tablet) dispersed in water under fasted conditions Treatment sequences were randomly assigned	Eight (8) total participants received each of the following treatments, with a 7-10 day washout period between treatments: Treatment A (taste assessment) = A single oral dose of RO7017773 (tablet) containing flavor/sweetener dispersed in water under fasted conditions Treatment B (taste assessment) = A single oral dose of RO7017773 (tablet) with no flavor/sweetener dispersed in apple juice under fasted conditions Treatment sequences were randomly assigned	Total of all reporting groups
Overall Participants	16	8	24
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	32.1 (9.66)	35.3 (10.57)	33.7 (4.44)
Sex: Female, Male (Count of Participants)
Female	0 0%	0 0%	0 0%
Male	16 100%	8 100%	24 100%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	4 25%	2 25%	6 25%
Not Hispanic or Latino	12 75%	6 75%	18 75%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	2 12.5%	0 0%	2 8.3%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	2 12.5%	0 0%	2 8.3%
White	12 75%	8 100%	20 83.3%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%

Outcome Measures

1. Primary Outcome

Title	Maximum Observed Plasma Concentration (Cmax) of RO7017773 (Part 1)
Time Frame	Day 1 to Day 5

Outcome Measure Data

Analysis Population Description

The PK population included all participants.

Arm/Group Title	Part 1 - Treatment A	Part 1 - Treatment B	Part 1 - Treatment C	Part 1 - Treatment D
Arm/Group Description	Participants received a single oral dose of RO7017773 (capsule) swallowed whole under fasted conditions	Participants received a single oral dose of RO7017773 (tablet) swallowed whole under fasted conditions	Participants received a single oral dose of RO7017773 (tablet) swallowed whole under fed conditions	Participants received a single oral dose of RO7017773 (tablet) dispersed in water under fasted conditions
Measure Participants	16	16	16	16
Geometric Mean (Geometric Coefficient of Variation) [ng/mL]	1320 (25.8)	1570 (27.4)	1120 (25.3)	1490 (26.6)

2. Secondary Outcome

Title	Taste Assessment, as Measured by Taste Questionnaire (Part 1)
Description	Taste was assessed using a questionnaire that asking participants to rate the overall taste of study drug dispersed in various vehicles on a scale from 1-5, with 1=no taste, and 5=very intense taste.
Time Frame	Day 1

Outcome Measure Data

Analysis Population Description

The population for this taste assessment was Part 1 - Treatment D (study drug dispersed in water).

Arm/Group Title	Part 1 - Treatment D
Arm/Group Description	Participants received a single oral dose of RO7017773 (tablet) dispersed in water under fasted conditions
Measure Participants	14
Median (Full Range) [Units on a Scale]	2

3. Primary Outcome

Title	Cmax of RO7017773 (Part 2)
Time Frame	Day 1 to Day 5

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Part 2 - Treatment A	Part 2 - Treatment B
Arm/Group Description	Participants received a single oral dose of RO7017773 (tablet) containing flavor/sweetener dispersed in water under fasted conditions	Participants received a single oral dose of RO7017773 (tablet) with no flavor/sweetener dispersed in apple juice under fasted conditions
Measure Participants	8	8
Geometric Mean (Geometric Coefficient of Variation) [ng/mL]	1470 (25.2)	1210 (19.0)

4. Primary Outcome

Title	Taste Assessment, as Measured by Taste Questionnaire (Part 2)
Description	Taste was assessed using a questionnaire that asking participants to rate the overall taste of study drug dispersed in various vehicles on a scale from 1-5, with 1=no taste, and 5=very intense taste.
Time Frame	Day 1

Outcome Measure Data

Analysis Population Description

The populations for this taste assessment were Part 2 - Treatment A and Part 2 - Treatment B.

Arm/Group Title	Part 2 - Treatment A	Part 2 - Treatment B
Arm/Group Description	Participants received a single oral dose of RO7017773 (tablet) containing flavor/sweetener dispersed in water under fasted conditions	Participants received a single oral dose of RO7017773 (tablet) with no flavor/sweetener dispersed in apple juice under fasted conditions
Measure Participants	8	8
Median (Full Range) [Units on a Scale]	3	1.5

5. Secondary Outcome

Title	Percentage of Participants With Adverse Events (AEs)
Time Frame	Baseline through end of study (approximately 6 weeks)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Part 1 - Treatment A	Part 1 - Treatment B	Part 1 - Treatment C	Part 1 - Treatment D	Part 2 - Treatment A	Part 2 - Treatment B
Arm/Group Description	Participants received a single oral dose of RO7017773 (capsule) swallowed whole under fasted conditions	Participants received a single oral dose of RO7017773 (tablet) swallowed whole under fasted conditions	Participants received a single oral dose of RO7017773 (tablet) swallowed whole under fed conditions	Participants received a single oral dose of RO7017773 (tablet) dispersed in water under fasted conditions	Participants received a single oral dose of RO7017773 (tablet) containing flavor/sweetener dispersed in water under fasted conditions	Participants received a single oral dose of RO7017773 (tablet) with no flavor/sweetener dispersed in apple juice under fasted conditions
Measure Participants	16	16	16	16	8	8
Number [Percentage of Participants]	56.3 351.9%	60.0 750%	53.3 222.1%	28.6 NaN	75.0 NaN	62.5 NaN

Adverse Events

Time Frame	Baseline through end of study (up to approximately 6 weeks)
Arm/Group Title	Part 1 - Treatment A		Part 1 - Treatment B		Part 1 - Treatment C		Part 1 - Treatment D		Part 2 - Treatment A		Part 2 - Treatment B
Arm/Group Description	Participants received a single oral dose of RO7017773 (capsule) swallowed whole under fasted conditions		Participants received a single oral dose of RO7017773 (tablet) swallowed whole under fasted conditions		Participants received a single oral dose of RO7017773 (tablet) swallowed whole under fed conditions		Participants received a single oral dose of RO7017773 (tablet) dispersed in water under fasted conditions		Participants received a single oral dose of RO7017773 (tablet) containing flavor/sweetener dispersed in water under fasted conditions		Participants received a single oral dose of RO7017773 (tablet) with no flavor/sweetener dispersed in apple juice under fasted conditions
All Cause Mortality
	Part 1 - Treatment A		Part 1 - Treatment B		Part 1 - Treatment C		Part 1 - Treatment D		Part 2 - Treatment A		Part 2 - Treatment B
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/16 (0%)		0/15 (0%)		0/15 (0%)		0/14 (0%)		0/8 (0%)		0/8 (0%)
Serious Adverse Events
	Part 1 - Treatment A		Part 1 - Treatment B		Part 1 - Treatment C		Part 1 - Treatment D		Part 2 - Treatment A		Part 2 - Treatment B
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/16 (0%)		0/15 (0%)		0/14 (0%)		0/14 (0%)		0/8 (0%)		0/8 (0%)
Other (Not Including Serious) Adverse Events
	Part 1 - Treatment A		Part 1 - Treatment B		Part 1 - Treatment C		Part 1 - Treatment D		Part 2 - Treatment A		Part 2 - Treatment B
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	9/16 (56.3%)		9/15 (60%)		8/15 (53.3%)		4/14 (28.6%)		6/8 (75%)		5/8 (62.5%)
Gastrointestinal disorders
Vomiting	2/16 (12.5%)	2	0/15 (0%)	0	1/15 (6.7%)	1	1/14 (7.1%)	1	0/8 (0%)	0	0/8 (0%)	0
Nausea	2/16 (12.5%)	2	1/15 (6.7%)	1	1/15 (6.7%)	2	1/14 (7.1%)	1	0/8 (0%)	0	0/8 (0%)	0
Flatulence	1/16 (6.3%)	1	1/15 (6.7%)	1	0/15 (0%)	0	0/14 (0%)	0	0/8 (0%)	0	0/8 (0%)	0
Diarrhoea	0/16 (0%)	0	0/15 (0%)	0	1/15 (6.7%)	1	1/14 (7.1%)	1	0/8 (0%)	0	0/8 (0%)	0
Constipation	0/16 (0%)	0	0/15 (0%)	0	1/15 (6.7%)	1	0/14 (0%)	0	0/8 (0%)	0	0/8 (0%)	0
Abdominal pain upper	1/16 (6.3%)	1	0/15 (0%)	0	0/15 (0%)	0	0/14 (0%)	0	0/8 (0%)	0	1/8 (12.5%)	1
General disorders
Pain	0/16 (0%)	0	0/15 (0%)	0	0/15 (0%)	0	1/14 (7.1%)	1	0/8 (0%)	0	0/8 (0%)	0
Fatigue	0/16 (0%)	0	0/15 (0%)	0	1/15 (6.7%)	1	0/14 (0%)	0	0/8 (0%)	0	0/8 (0%)	0
Infections and infestations
Upper respiratory tract infection	0/16 (0%)	0	0/15 (0%)	0	0/15 (0%)	0	1/14 (7.1%)	1	0/8 (0%)	0	0/8 (0%)	0
Injury, poisoning and procedural complications
Skin laceration	0/16 (0%)	0	1/15 (6.7%)	1	0/15 (0%)	0	0/14 (0%)	0	0/8 (0%)	0	0/8 (0%)	0
Investigations
Blood pressure increased	1/16 (6.3%)	1	0/15 (0%)	0	0/15 (0%)	0	0/14 (0%)	0	0/8 (0%)	0	0/8 (0%)	0
Blood creatinine increased	0/16 (0%)	0	1/15 (6.7%)	1	0/15 (0%)	0	0/14 (0%)	0	0/8 (0%)	0	0/8 (0%)	0
Blood creatine phosphokinase increased	0/16 (0%)	0	0/15 (0%)	0	1/15 (6.7%)	1	0/14 (0%)	0	0/8 (0%)	0	0/8 (0%)	0
Metabolism and nutrition disorders
Decreased appetite	0/16 (0%)	0	0/15 (0%)	0	1/15 (6.7%)	1	0/14 (0%)	0	0/8 (0%)	0	0/8 (0%)	0
Musculoskeletal and connective tissue disorders
Myalgia	0/16 (0%)	0	0/15 (0%)	0	0/15 (0%)	0	0/14 (0%)	0	0/8 (0%)	0	0/8 (0%)	0
Nervous system disorders
Somnolence	2/16 (12.5%)	2	2/15 (13.3%)	2	3/14 (21.4%)	3	1/14 (7.1%)	1	5/8 (62.5%)	5	2/8 (25%)	2
Headache	4/16 (25%)	5	4/15 (26.7%)	4	2/15 (13.3%)	2	1/14 (7.1%)	1	3/8 (37.5%)	3	4/8 (50%)	4
Dizziness	1/16 (6.3%)	1	1/15 (6.7%)	1	1/15 (6.7%)	1	2/14 (14.3%)	2	2/8 (25%)	2	1/8 (12.5%)	1
Psychomotor hyperactivity	0/16 (0%)	0	0/15 (0%)	0	1/15 (6.7%)	1	0/14 (0%)	0	0/8 (0%)	0	0/8 (0%)	0
Sleep paralysis	0/16 (0%)	0	0/15 (0%)	0	0/15 (0%)	0	0/14 (0%)	0	1/8 (12.5%)	1	0/8 (0%)	0
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain	0/16 (0%)	0	1/15 (6.7%)	1	1/15 (6.7%)	1	1/14 (7.1%)	1	0/8 (0%)	0	0/8 (0%)	0
Rhinorrhoea	0/16 (0%)	0	0/15 (0%)	0	1/15 (6.7%)	1	1/14 (7.1%)	1	0/8 (0%)	0	0/8 (0%)	0
Nasal congestion	0/16 (0%)	0	1/15 (6.7%)	1	0/15 (0%)	0	0/14 (0%)	0	0/8 (0%)	0	0/8 (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.