Escalating Dose Study in Healthy Volunteers With SEN0014196

• Register: ClinicalTrials.gov
• Last refreshed on: 19 February 2015
• Main ID: NCT01521832
• Date of registration: 13/01/2012
• Prospective Registration: No
• Primary sponsor: Siena Biotech S.p.A.
• Public title: Escalating Dose Study in Healthy Volunteers With SEN0014196
• Scientific title: A Phase I, Randomised, Double-Blind, Placebo-Controlled, Two-Part Study Consisting of Single and Multiple Oral Dose Escalation to Determine, Safety, Tolerability and Pharmacokinetics of SEN0014196
• Date of first enrolment: October 2009
• Target sample size: 88
• Recruitment status: Completed
• URL: http://clinicaltrials.gov/show/NCT01521832
• Study type: Interventional
• Study design: Allocation: Randomized, Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Treatment
• Phase: Phase 1

Countries of recruitment

United Kingdom

Contacts

• Name: Joseph A Chiesa, MD
• Affiliation: Covance Clinical Research Unit Ltd.

Key inclusion & exclusion criteria

Inclusion Criteria:

- Subjects in Groups A to G and Groups I to K will be males of any ethnic origin
between 18 and 55 years of age and with a body mass index (BMI) between 18 and 31
kg/m2 inclusive. Subjects in Groups H and L will be females of any ethnic origin
between 18 and 65 years of age and with a body mass index (BMI) between 18 and 31
kg/m2 inclusive. All subjects will have a body weight greater than 50 kg. For Group
H, women will be of non-childbearing potential, defined as follows: Female subjects
50 years of age or less must be surgically sterile or post-menopausal (defined as at
least two years post cessation of menses and/or follicular stimulating hormone >18
mIU/mL and serum oestradiol <110 pmol/L), non-lactating and have a negative serum
pregnancy test Female subjects of more than 51 years of age must be surgically
sterile or post-menopausal (defined by a value of follicular stimulating hormone >18
mIU/mL and no spontaneous menstruation for at least one year before the first dose),
non-lactating and have a negative serum pregnancy test.

- Subjects must be in good health, as determined by a medical history, physical
examination, 12-lead electrocardiogram (ECG) and clinical laboratory evaluations
Note: congenital non-haemolytic hyperbilirubinaemia is not acceptable and serum
potassium must be within the normal reference ranges (confirmed by repeat analysis).

- Subjects will have given their written informed consent to participate in the study
and to abide by the study restrictions.

Exclusion Criteria:

- Male subjects or Female subjects in Group H who are not, or whose partners are not
willing to use appropriate contraception (such as condom) with spermicidal
foam/gel/film/cream/suppository) from the time of the first dose until 3 months after
the final dosing occasion. Female subjects in Group L who are not, willing to use
appropriate contraception (such as condom) with spermicidal
foam/gel/film/cream/suppository) from the time of screening until 3 months after the
final dosing occasion, who have not had a menstrual period in the 28 days before the
first dose.

- Subjects who have received any prescribed systemic or topical medication within 14
days of the first dose administration (for female subjects, stable hormone
replacement therapy is acceptable) unless in the opinion of the Investigator the
medication will not interfere with the study procedures or compromise safety.

- Subjects who have used any non-prescribed systemic or topical medication (including
herbal remedies) within 7 days of the first dose administration (with the exception
of vitamin/mineral supplements) unless in the opinion of the Investigator the
medication will not interfere with the study procedures or compromise safety.

- Subjects who have received any medications, including St John's Wort, known to
chronically alter drug absorption or elimination processes within 30 days of the
first dose administration unless in the opinion of the Investigator the medication
will not interfere with the study procedures or compromise safety

- Subjects who are still participating in a clinical study (e.g. attending follow-up
visits) or who have participated in a clinical study involving administration of an
investigational drug (new chemical entity) in the past 3 months, where possible this
will be confirmed using The Over Volunteering Protection Service (TOPS).

- Subjects who have donated any blood, plasma or platelets in the 2 months prior to
screening or who have made donations on more than two occasions within the 12 months
preceding the first dose administration.

- Subjects with a significant history of drug allergy as determined by the
Investigator.

- Subjects who have any clinically significant allergic disease (excluding non-active
hayfever) as determined by the Investigator.

- Subjects who have a supine blood pressure and supine pulse rate higher than 140/90
mmHg and 100 beats per minute (bpm), respectively, or lower than 90/50 mmHg and 40
bpm, respectively, confirmed by a repeat assessment.

- Subjects who consume more than 28 units (males) or more than 21 units (females) of
alcohol per week or who have a significant history of alcoholism or drug/chemical
abuse as determined by the Investigator (one unit of alcohol equals ½ pint [285 mL]
of beer or lager, one glass [125 mL] of wine, or 1/6 gill [25 mL] of spirits).

- Subjects with a positive urine drug screen or alcohol breath test result at screening
or first admission. Or a history of substance abuse in the last 12 months prior to
the start of the study.

- Subjects who smoke more than 5 cigarettes or the equivalent in tobacco per day.

- Subjects with, or with a history of, any clinically significant neurological,
gastrointestinal, renal, hepatic, cardiovascular, psychiatric, respiratory,
metabolic, endocrine, haematological or other major disorders as determined by the
Investigator.

- Subjects with, or with a family history of Huntington's Disease

- Subjects who have previously received histone deacetylase inhibitors e.g. vorinostat
(Zolinza®) or have participated in a clinical trial using a histone deacetylase
inhibitor.

- Subjects who have had a clinically significant illness within 4 weeks of the start of
dose administration as determined by the Investigator

- Subjects who are known to have serum hepatitis, or who are carriers of the hepatitis
B surface antigen (HBsAg) or hepatitis C antibody, or who have a positive result to
the test for HIV antibodies.

- Subjects who have an abnormality in the 12-lead ECG that, in the opinion of the
investigator, increases the risk of participating in the study, such as QTcF interval
>450 msec (male) or greater than 470msec (female), or with sinus rhythm with PR
interval <110 msec or >240 msec, confirmed by a repeat ECG.

- Subjects who, in the opinion of the Investigator, should not participate in the
study.



Age minimum: 18 Years
Age maximum: 65 Years
Gender: Both

Health Condition(s) or Problem(s) studied

Huntington's Disease

Intervention(s)

Drug: SEN0014196

Primary Outcome(s)

Safety and tolerability of ascending single and multiple oral doses of SEN0014196 in healthy male and female subjects. [Time Frame: Up to 7 days after single dose and up to 10 days following multiple dose]

Secondary Outcome(s)

Single and multiple dose pharmacokinetics of SEN0014196 [Time Frame: Up to 96 hours following single dose and up to 48 hours following multiple dose.]

Secondary ID(s)

S015-001

Source(s) of Monetary Support

Please refer to primary and secondary sponsors