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

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

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).

Study Overview

• Status: Completed
• Conditions: Huntington's Disease
• Intervention / Treatment: Drug: SEN0014196

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.

• Study Type: Interventional
• Enrollment (Actual): 26
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • La Jolla, California, United States, 92037-0706
      • University of California San Diego
    • Sacramento, California, United States, 95655
      • University of California Davis Medical Center
  • Missouri
    • St. Louis, Missouri, United States, 63110
      • Washington University
  • New York
    • Rocherster, New York, United States, 14627
      • University of Rochester
  • North Carolina
    • Winston-Salem, North Carolina, United States, 27157-1078
      • Wake Forest School of Medicine
  • Texas
    • Dallas, Texas, United States, 75390-8527
      • University of Texas Southwestern Medical Center
    • Houston, Texas, United States, 77030
      • Baylor College of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 25 years to 65 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Fasted condition; 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.	Drug: SEN0014196; 100 mg, immediate release tablets, once daily administration
EXPERIMENTAL: Fed condition; Subjects in the Fed group will take study drug within 30 minutes after starting breakfast; these subjects will otherwise maintain their normal eating schedule.	Drug: SEN0014196; 100 mg, immediate release tablets, once daily administration

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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).	14 Days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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]).	14 Days
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.	14 Days

Collaborators and Investigators

• Sponsor: Siena Biotech S.p.A.
• Investigators: Principal Investigator: Francis O Walker, MD, Wake Forest University Health Sciences

Study record dates

Study Major Dates

• Study Start: November 1, 2011
• Primary Completion (ACTUAL): November 1, 2012
• Study Completion (ACTUAL): December 1, 2012

Study Registration Dates

• First Submitted: November 29, 2011
• First Submitted That Met QC Criteria: December 5, 2011
• First Posted (ESTIMATE): December 6, 2011

Study Record Updates

• Last Update Posted (ESTIMATE): March 20, 2013
• Last Update Submitted That Met QC Criteria: March 19, 2013
• Last Verified: March 1, 2013

More Information

Terms related to this study

• Keywords: Nervous System Diseases; Dementia; Movement Disorders; Central Nervous System Diseases; Genetic Diseases, Inborn; Neurodegenerative Diseases; Huntington Disease; Mental Disorders; Cognition Disorders; Brain Diseases; Dyskinesias; Basal Ganglia Diseases; Chorea; Heredodegenerative Disorders, Nervous System
• Additional Relevant MeSH Terms: Mental Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurocognitive Disorders; Genetic Diseases, Inborn; Basal Ganglia Diseases; Movement Disorders; Neurodegenerative Diseases; Dyskinesias; Heredodegenerative Disorders, Nervous System; Dementia; Cognition Disorders; Chorea; Huntington Disease
• Other Study ID Numbers: S015-007