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

Sponsor

Siena Biotech S.p.A. (Industry)

Overall Status

Completed

CT.gov ID

NCT01485965

Collaborator

(none)

Enrollment

Locations

Arms

Duration (Months)

3.7

Patients Per Site

0.3

Patients Per Site Per Month

Study Details

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).

Condition or Disease	Intervention/Treatment	Phase
Huntington's Disease	Drug: SEN0014196	Phase 1

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 Design

Study Type:

Interventional

Actual Enrollment :

26 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (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

Study Start Date :

Nov 1, 2011

Actual Primary Completion Date :

Nov 1, 2012

Actual Study Completion Date :

Dec 1, 2012

Arms and Interventions

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

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

Outcome Measures

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 [14 Days]
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 [14 Days]
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 [14 Days]
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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

25 Years to 65 Years

Sexes Eligible for Study:

All

Accepts 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of California San Diego	La Jolla	California	United States	92037-0706
2	University of California Davis Medical Center	Sacramento	California	United States	95655
3	Washington University	St. Louis	Missouri	United States	63110
4	University of Rochester	Rocherster	New York	United States	14627
5	Wake Forest School of Medicine	Winston-Salem	North Carolina	United States	27157-1078
6	University of Texas Southwestern Medical Center	Dallas	Texas	United States	75390-8527
7	Baylor College of Medicine	Houston	Texas	United States	77030