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

Huntington's Disease Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01485965
• Other study ID #: S015-007
• Status: Completed
• Phase: Phase 1
• First received: November 29, 2011
• Last updated: March 19, 2013
• Start date: November 2011
• Est. completion date: December 2012

Study information

• Verified date: March 2013
• Source: Siena Biotech S.p.A.
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 26
• Est. completion date: December 2012
• Est. primary completion date: November 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 25 Years to 65 Years

Eligibility

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 Design

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

Related Conditions & MeSH terms

• Huntington Disease
• Huntington's Disease

Intervention

Drug:
• SEN0014196
100 mg, immediate release tablets, once daily administration

Locations

Country	Name	City	State
United States	University of Texas Southwestern Medical Center	Dallas	Texas
United States	Baylor College of Medicine	Houston	Texas
United States	University of California San Diego	La Jolla	California
United States	University of Rochester	Rocherster	New York
United States	University of California Davis Medical Center	Sacramento	California
United States	Washington University	St. Louis	Missouri
United States	Wake Forest School of Medicine	Winston-Salem	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Siena Biotech S.p.A.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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-t), AUC from time zero to the last quantifiable concentration (AUC0-last), AUC from time zero to infinity (AUC0-8), terminal elimination half-life (t1/2), and terminal elimination rate constant (?z).	14 Days	No
Secondary	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	No
Secondary	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	Yes