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A Open-label Food Effect Study With SEN0014196 in Subjects With Huntington Disease

Primary Purpose

Huntington's Disease

Status

Completed

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

SEN0014196

About this trial

This is an interventional treatment trial for Huntington's Disease focused on measuring Huntington Disease, Basal Ganglia Diseases, Brain Diseases, Central Nervous System Diseases, Nervous System Diseases, Dementia, Chorea, Dyskinesias, Movement Disorders, Heredodegenerative Disorders, Nervous System, Neurodegenerative Diseases, Genetic Diseases, Inborn, Cognition Disorders, Mental Disorders

Eligibility Criteria

25 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Subjects with early to mid HD, i.e., genetically confirmed HD (cytosine, adenine, guanine [CAG] codon repeat length ≥ 36), motor signs of HD, and a Total Functional Capacity Subscale Score (TFC) ≥ 7
Body mass index between 18 and 31 kg/m2 inclusive
All subjects must have a body weight greater than 50 kg
Female subjects must be surgically sterile, postmenopausal, or willing to practice a highly effective method of contraception. All female participants must be nonlactating and nonpregnant. Male subjects must agree to use a reliable method of birth control during the study and for 3 months after the last dose of study drug.
Capable of providing informed consent
MMSE ≥24
Subjects must have a live-in competent observer

Exclusion Criteria:

Participation in a study or received an investigational drug within 30 days of the Baseline Visit
Any prior or concomitant use of compounds suspected of interfering with protein acetylation
Any concomitant use of medications that are known inhibitors of CYP450 enzymes or substrates of CYP1A2 at the time of enrollment
Suicide risk, as determined by meeting either of the following criteria: a) a suicide attempt within the past year or suicidal ideation within 60 days of the Screening Visit; b) Significant risk of suicide, as judged by the Investigator
Subjects with MMSE < 24
Subjects with presence of clinically significant psychosis and/or confusional states, in the opinion of the Investigator
Subjects with clinically significant laboratory or ECG abnormalities at Screening or Baseline
Subjects with clinically relevant hematologic, hepatic, cardiac, or renal disease
Subjects with a current or past (within the last 12 months) history of epilepsy or seizures
A medical history of infection with human immunodeficiency virus, hepatitis C, and/or hepatitis B
Subjects with a history of substance abuse within the past 12 months
Female subjects who are pregnant or breastfeeding
Known allergy to any ingredient in the study drug
A history of malignancy of any type within 2 years prior to Screening. A history of surgically-excised nonmelanoma skin cancers is permitted.
Any relevant condition, behavior, laboratory value, or concomitant medication which, in the opinion of the Investigator, makes the subject unsuitable for entry into the study

Sites / Locations

University of California San Diego
University of California Davis Medical Center
Washington University
University of Rochester
Wake Forest School of Medicine
University of Texas Southwestern Medical Center
Baylor College of Medicine

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Arm Label

Fasted condition

Fed condition

Arm Description

Subjects in the Fasted group will take study drug after an overnight fast (since at least midnight). Additionally, on PK assessment days, no food will be allowed for at least 4 hours after study drug administration.

Subjects in the Fed group will take study drug within 30 minutes after starting breakfast; these subjects will otherwise maintain their normal eating schedule.

Outcomes

Primary Outcome Measures

To determine the effect of food on the repeated dose pharmacokinetics of SEN0014196 at 100 mg once daily in subjects with Huntington's disease

The effect of food on the PK of SEN0014196 will be evaluated for the following parameters: maximum observed plasma concentration (Cmax), time of maximum observed plasma concentration(tmax), AUC from time zero to the length of the dosing interval (tau) (AUC0-τ), AUC from time zero to the last quantifiable concentration (AUC0-last), AUC from time zero to infinity (AUC0-∞), terminal elimination half-life (t1/2), and terminal elimination rate constant (λz).

Secondary Outcome Measures

Pharmacodynamics

The following PD biomarkers will be assessed: soluble huntingtin levels and huntingtin acetylation status (by enzyme-linked immunosorbent assay [ELISA] and liquid chromatography-tandem mass spectrometry [LC-MS/MS]).

To determine the safety and tolerability of repeated doses of SEN0014196 at 100 mg once daily in subjects with Huntington's disease

Safety assessments include: AEs, ECGs, vital signs, body weight and height, clinical laboratory evaluations (serum biochemistry and hematology), urinalysis, physical and neurological examinations, C-SSRS, and UHDRS.

Full Information

NCT ID

NCT01485965

First Posted

November 29, 2011

Last Updated

March 19, 2013

Sponsor

Siena Biotech S.p.A.

1. Study Identification

Unique Protocol Identification Number

NCT01485965

Brief Title

A Open-label Food Effect Study With SEN0014196 in Subjects With Huntington Disease

Official Title

A Phase 1b, Open-label, Parallel-group Study in Subjects With Huntington Disease to Assess the Safety, Tolerability, and Fed/Fasted Pharmacokinetics of Repeated Oral Doses of SEN0014196

Study Type

Interventional

2. Study Status

Record Verification Date

March 2013

Overall Recruitment Status

Completed

Study Start Date

November 2011 (undefined)

Primary Completion Date

November 2012 (Actual)

Study Completion Date

December 2012 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Siena Biotech S.p.A.

4. Oversight

Data Monitoring Committee

5. Study Description

Brief Summary

The primary purpose of this study is to assess the effect of food upon the pharmacokinetics (PK) of SEN0014196 in subjects with Huntington disease (HD).

Detailed Description

In addition to the pharmacokinetic endpoints, the study will assess the safety and tolerability of 100 mg once daily (qd) doses of SEN0014196 over 14 days in subjects with HD and explore potential biomarkers for use in subsequent Phase 2/3 studies.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Huntington's Disease

Keywords

Huntington Disease, Basal Ganglia Diseases, Brain Diseases, Central Nervous System Diseases, Nervous System Diseases, Dementia, Chorea, Dyskinesias, Movement Disorders, Heredodegenerative Disorders, Nervous System, Neurodegenerative Diseases, Genetic Diseases, Inborn, Cognition Disorders, Mental Disorders

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

26 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Fasted condition

Arm Type

Experimental

Arm Description

Arm Title

Fed condition

Arm Type

Experimental

Arm Description

Subjects in the Fed group will take study drug within 30 minutes after starting breakfast; these subjects will otherwise maintain their normal eating schedule.

Intervention Type

Drug

Intervention Name(s)

SEN0014196

Intervention Description

100 mg, immediate release tablets, once daily administration

Primary Outcome Measure Information:

Title

To determine the effect of food on the repeated dose pharmacokinetics of SEN0014196 at 100 mg once daily in subjects with Huntington's disease

Description

Time Frame

14 Days

Secondary Outcome Measure Information:

Title

Pharmacodynamics

Description

Time Frame

14 Days

Title

To determine the safety and tolerability of repeated doses of SEN0014196 at 100 mg once daily in subjects with Huntington's disease

Description

Time Frame

14 Days

10. Eligibility

Sex

All

Minimum Age & Unit of Time

25 Years

Maximum Age & Unit of Time

65 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Subjects with early to mid HD, i.e., genetically confirmed HD (cytosine, adenine, guanine [CAG] codon repeat length ≥ 36), motor signs of HD, and a Total Functional Capacity Subscale Score (TFC) ≥ 7 Body mass index between 18 and 31 kg/m2 inclusive All subjects must have a body weight greater than 50 kg Female subjects must be surgically sterile, postmenopausal, or willing to practice a highly effective method of contraception. All female participants must be nonlactating and nonpregnant. Male subjects must agree to use a reliable method of birth control during the study and for 3 months after the last dose of study drug. Capable of providing informed consent MMSE ≥24 Subjects must have a live-in competent observer Exclusion Criteria: Participation in a study or received an investigational drug within 30 days of the Baseline Visit Any prior or concomitant use of compounds suspected of interfering with protein acetylation Any concomitant use of medications that are known inhibitors of CYP450 enzymes or substrates of CYP1A2 at the time of enrollment Suicide risk, as determined by meeting either of the following criteria: a) a suicide attempt within the past year or suicidal ideation within 60 days of the Screening Visit; b) Significant risk of suicide, as judged by the Investigator Subjects with MMSE < 24 Subjects with presence of clinically significant psychosis and/or confusional states, in the opinion of the Investigator Subjects with clinically significant laboratory or ECG abnormalities at Screening or Baseline Subjects with clinically relevant hematologic, hepatic, cardiac, or renal disease Subjects with a current or past (within the last 12 months) history of epilepsy or seizures A medical history of infection with human immunodeficiency virus, hepatitis C, and/or hepatitis B Subjects with a history of substance abuse within the past 12 months Female subjects who are pregnant or breastfeeding Known allergy to any ingredient in the study drug A history of malignancy of any type within 2 years prior to Screening. A history of surgically-excised nonmelanoma skin cancers is permitted. Any relevant condition, behavior, laboratory value, or concomitant medication which, in the opinion of the Investigator, makes the subject unsuitable for entry into the study

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Francis O Walker, MD

Organizational Affiliation

Wake Forest University Health Sciences

Official's Role

Principal Investigator

Facility Information:

Facility Name

University of California San Diego

City

La Jolla

State/Province

California

ZIP/Postal Code

92037-0706

Country

United States

Facility Name

University of California Davis Medical Center

City

Sacramento

State/Province

California

ZIP/Postal Code

95655

Country

United States

Facility Name

Washington University

City

St. Louis

State/Province

Missouri

ZIP/Postal Code

63110

Country

United States

Facility Name

University of Rochester

City

Rocherster

State/Province

New York

ZIP/Postal Code

14627

Country

United States

Facility Name

Wake Forest School of Medicine

City

Winston-Salem

State/Province

North Carolina

ZIP/Postal Code

27157-1078

Country

United States

Facility Name

University of Texas Southwestern Medical Center

City

Dallas

State/Province

Texas

ZIP/Postal Code

75390-8527

Country

United States

Facility Name

Baylor College of Medicine

City

Houston

State/Province

Texas

ZIP/Postal Code

77030

Country

United States

12. IPD Sharing Statement

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A Open-label Food Effect Study With SEN0014196 in Subjects With Huntington Disease

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