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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Siena Biotech S.p.A.
ClinicalTrials.gov Identifier:
NCT01485965
First received: November 29, 2011
Last updated: March 19, 2013
Last verified: March 2013
History of Changes
  Purpose

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).


Condition Intervention Phase
Huntington's Disease
 Drug: SEN0014196
 Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by Siena Biotech S.p.A.:

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 [ Time Frame: 14 Days ] [ Designated as safety issue: No ]
    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 [ Time Frame: 14 Days ] [ Designated as safety issue: No ]
    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 [ Time Frame: 14 Days ] [ Designated as safety issue: Yes ]
    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.


Enrollment: 26
Study Start Date: November 2011
Study Completion Date: December 2012
Primary Completion Date: November 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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.

  Eligibility

Ages Eligible for Study:   25 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01485965

Locations
United States, California
University of California San Diego
La Jolla, California, United States, 92037-0706
University of California Davis Medical Center
Sacramento, California, United States, 95655
United States, Missouri
Washington University
St. Louis, Missouri, United States, 63110
United States, New York
University of Rochester
Rocherster, New York, United States, 14627
United States, North Carolina
Wake Forest School of Medicine
Winston-Salem, North Carolina, United States, 27157-1078
United States, Texas
University of Texas Southwestern Medical Center
Dallas, Texas, United States, 75390-8527
Baylor College of Medicine
Houston, Texas, United States, 77030
Sponsors and Collaborators
Siena Biotech S.p.A.
Investigators
Principal Investigator: Francis O Walker, MD Wake Forest School of Medicine
  More Information

No publications provided

Responsible Party: Siena Biotech S.p.A.
ClinicalTrials.gov Identifier: NCT01485965     History of Changes
Other Study ID Numbers: S015-007
Study First Received: November 29, 2011
Last Updated: March 19, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Siena Biotech S.p.A.:
Huntington Disease
Basal Ganglia Diseases
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Movement Disorders
Heredodegenerative Disorders, Nervous System
 Neurodegenerative Diseases
Genetic Diseases, Inborn
Cognition Disorders
Mental Disorders
Dementia
Chorea
Dyskinesias

Additional relevant MeSH terms:
Huntington Disease
Basal Ganglia Diseases
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Movement Disorders
Heredodegenerative Disorders, Nervous System
Neurodegenerative Diseases
 Genetic Diseases, Inborn
Cognition Disorders
Delirium, Dementia, Amnestic, Cognitive Disorders
Mental Disorders
Dementia
Chorea
Dyskinesias

ClinicalTrials.gov processed this record on May 23, 2013