Safety and Pharmacology Study of VP 20629 in Adults With... | NCT01898884

NCT01898884

Protocol Section

Identification Module

Results Section

Participant Flow Module

Annotation Section

No data available

No data is available for this block.

Document Section

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No data is available for this block.

Derived Section

Miscellaneous Info Module

Status Module

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Single dose of VP 20629 or placebo	Experimental	Four groups of 8 subjects each will receive a single dose of VP 20629 (150 mg, 450 mg, 900 mg, or 1200 mg) or placebo.	Drug: VP 20629 Drug: Placebo
Multiple doses of VP 20629 or placebo	Experimental	Three groups of 8 subjects each will receive multiple doses of VP 20629 (300 mg, 600 mg, or 900 mg total daily dose) or placebo. VP 20629 or placebo will be administered every 8 hours for 7 days with a single morning dose on Day 8.	Drug: VP 20629 Drug: Placebo

Name	Type	Description	Arm Group Labels	Other Names
VP 20629	Drug		Multiple doses of VP 20629 or placebo Single dose of VP 20629 or placebo	Indole-3-propionic acid

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs)	An adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A serious adverse event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged in-patient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent AEs (TEAEs), defined as all AEs that start during study drug treatment (and up to 7 days after the last dose of the study drug) and were not seen at baseline, or were seen at baseline but increased in frequency and/or severity during study drug treatment (and up to 7 days after the last dose of study drug).	From Start of Study Treatment up to Day 19
Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs)	An abnormal laboratory finding which required an action or intervention by the investigator, or a finding judged by the investigator to represent a change beyond the range of normal physiologic fluctuation were reported as an adverse event. Treatment-emergent were events between first dose of study drug and 7 days after the last dose that were absent before treatment or that worsened relative to pretreatment state. Number of participants with Grade 3 or higher treatment-emergent adverse events for laboratory abnormalities were reported as clinically relevant laboratory changes.	From Start of Study Treatment up to Day 19
Number of Participants With Vital Signs Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs)	Vital sign assessments included systolic blood pressure, diastolic blood pressure, heart rate, and temperature. Vital signs abnormalities reported as TEAEs were reported.	From Start of Study Treatment up to Day 19
Number of Participants With Clinically Relevant Electrocardiogram (ECG) Abnormalities Recorded as Adverse Events (AEs)

Secondary Outcomes

Measure	Description	Time Frame
Maximum Observed Serum Concentration (Cmax) of VP 20629 and Its Metabolite (VP 20631) for Single Dose Groups	The Cmax is the maximum observed plasma concentration of single dose of VP 20629 and VP 20631.	Predose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8,10, 12, 24 and 48 hours Postdose on Day 1
Time of Maximum Observed Plasma Concentration (Tmax) of VP 20629 and Its Metabolite (VP 20631) for Single Dose Groups

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Be 18 to 45 years of age (inclusive).
Have a body mass index between 18 and 27 kg/m^2 (inclusive).
Have a clinical presentation consistent with FA.
Have a confirmed diagnosis of FA with a defined expanded guanosine, adenine, adenine (GAA) triplet repeat number.
Have an International Cooperative Ataxia Rating Scale (ICARS) mean total score of ≤75.
If female, be postmenopausal (cessation of menses ≥1 year), surgically sterile, or have a negative serum human chorionic gonadotropin pregnancy test within 5 days prior to the first dose of study drug. Women of child bearing potential must also be on an acceptable method of birth control, as determined by the Investigator, for 3 months prior to the first dose and must agree to continue use through 2 months after the last dose of study drug.

If male, be surgically sterile or agree to follow an acceptable method of birth control as determined by the Investigator, from the screening visit through 2 months after the last dose of study drug.
Be able to swallow capsules whole.
Agree to adhere to the protocol-defined schedule of assessments and procedures.
Be informed of the nature of the study and provide written informed consent before any study-specific procedures are performed.

Exclusion Criteria:

Have taken coenzyme Q10, idebenone, other dietary or herbal supplements (with an anti-oxidative effect), or over-the-counter medications (including homeopathic medicines and vitamins) within 1 week prior to the first dose of study drug on Day 1.
If female, be pregnant or breastfeeding.
Have a positive test result for human immunodeficiency virus (HIV), hepatitis B surface antigen, or hepatitis C antibody.
Have ingested any alcohol within 48 hours before admission to the clinical study unit on Day -1. NOTE: Caffeine intake should be limited to 2 caffeine-containing beverages per day during this same time period.
Have participated in an investigational drug trial within 30 days prior to the first dose of study drug on Day 1. NOTE: Subjects who received study drug (VP 20629 or placebo) in a single-dose group in this study and completed the Post-treatment Safety Assessment are allowed to enroll in a multiple-dose group following a 21 day washout period, provided they continue to meet protocol eligibility criteria. Subjects cannot enroll in a multiple-dose group if they have an ongoing adverse event following participation in a single-dose group or had a serious adverse event during a single-dose group (regardless of causality).
Have a known hypersensitivity to any ingredient in the study formulation.
Have, as determined by the Investigator and/or medical monitor, any clinically relevant medical or surgical condition that could interfere with the administration of study drug, interpretation of study results, or compromise the safety or well-being of the subject.
Have a Columbia-Suicide Severity Rating Scale (C-SSRS) score of 4 or 5.

Name	Affiliation	Role
Study Director	Takeda	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
UCLA Medical Center		Los Angeles	California	90095	United States
University of South Florida

Arm/Group Information

ID	Title	Description
FG000	Single Dose Placebo	Participants received placebo matching to single dose of VP 20629 capsules orally under fasting condition on Day 1.
FG001	Single Dose VP 20629 150 mg	Participants received single dose of VP 20629 capsules of 150 milligram (mg) orally under fasting condition on Day 1.
FG002	Single Dose VP 20629 450 mg	Participants received single dose of VP 20629 capsules of 450 mg orally under fasting condition on Day 1.
FG003	Single Dose VP 20629 900 mg	Participants received single dose of VP 20629 capsules of 900 mg orally under fasting condition on Day 1.
FG004	Single Dose VP 20629 1200 mg	Participants received single dose of VP 20629 capsules of 1200 mg orally under fasting condition on Day 1.
FG005	Multiple Dose Placebo	Participants received placebo matching to multiple doses of VP 20629 capsules orally daily from Day 1 to Day 8 morning under fasting conditions.
FG006	Multiple Dose VP 20629 300 mg	Participants received VP 20629 capsules 300 mg total daily dose in 3 divided doses (100 mg every 8 hours) orally daily from Day 1 to Day 8 morning under fasting conditions.
FG007	Multiple Dose VP 20629 600 mg	Participants received VP 20629 capsules 600 mg total daily dose in 3 divided doses (200 mg every 8 hours) orally daily from Day 1 to Day 8 morning under fasting conditions.
FG008	Multiple Dose VP 20629 900 mg	Participants received VP 20629 capsules 900 mg total daily dose in 3 divided doses (300 mg every 8 hours) orally daily from Day 1 to Day 8 morning under fasting conditions.

Baseline Characteristics Module

Arm/Group Information

ID	Title	Description
BG000	Single Dose Placebo	Participants received placebo matching to single dose of VP 20629 capsules orally under fasting condition on Day 1.
BG001	Single Dose VP 20629 150 mg	Participants received single dose of VP 20629 capsules of 150 milligram (mg) orally under fasting condition on Day 1.

Units	Counts
Participants	BG000

Title	Description	Population Description	Parameter Type	Dispersion Type	Unit of Measure	Calculate Percentage	Denominator Units Selected	Denominators	Classes
Age, Continuous			Mean

Outcome Measures Module

Outcome Measures

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs)

An adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A serious adverse event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged in-patient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent AEs (TEAEs), defined as all AEs that start during study drug treatment (and up to 7 days after the last dose of the study drug) and were not seen at baseline, or were seen at baseline but increased in frequency and/or severity during study drug treatment (and up to 7 days after the last dose of study drug).

The ITT-safety (ITT-S) set consisted of all participants who were randomly assigned to an investigational product treatment group and who received at least 1 partial or complete dose of investigational product.

Posted

Number

participants

From Start of Study Treatment up to Day 19

Adverse Events Module

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Single Dose Placebo	Participants received placebo matching to single dose of VP 20629 capsules orally under fasting conditions on Day 1.

ID	Term
D013132	Spinocerebellar Degenerations
D002526	Cerebellar Diseases
D001927	Brain Diseases
D002493	Central Nervous System Diseases

OG000	Single Dose Placebo	Participants received placebo matching to single dose of VP 20629 capsules orally under fasting condition on Day 1.
OG001	Single Dose VP 20629 150 mg	Participants received single dose of VP 20629 capsules of 150 milligram (mg) orally under fasting condition on Day 1.
OG002	Single Dose VP 20629 450 mg	Participants received single dose of VP 20629 capsules of 450 mg orally under fasting condition on Day 1.
OG003	Single Dose VP 20629 900 mg	Participants received single dose of VP 20629 capsules of 900 mg orally under fasting condition on Day 1.
OG004	Single Dose VP 20629 1200 mg	Participants received single dose of VP 20629 capsules of 1200 mg orally under fasting condition on Day 1.
OG005	Multiple Dose Placebo	Participants received placebo matching to multiple doses of VP 20629 capsules orally daily from Day 1 to Day 8 morning under fasting conditions.
OG006	Multiple Dose VP 20629 300 mg	Participants received VP 20629 capsules 300 mg total daily dose in 3 divided doses (100 mg every 8 hours) orally daily from Day 1 to Day 8 morning under fasting conditions.
OG007	Multiple Dose VP 20629 600 mg	Participants received VP 20629 capsules 600 mg total daily dose in 3 divided doses (200 mg every 8 hours) orally daily from Day 1 to Day 8 morning under fasting conditions.
OG008	Multiple Dose VP 20629 900 mg	Participants received VP 20629 capsules 900 mg total daily dose in 3 divided doses (300 mg every 8 hours) orally daily from Day 1 to Day 8 morning under fasting conditions.