A Single Dose PK Study of SENS-218 in Healthy Volunteers

An Open-label, Single-dose, Pharmacokinetic Study of SENS-218 in Healthy Adult, Caucasian Subjects.

This study is to aid the development for the use of SENS-218 outside its marketed therapeutic indications. SENS-218 is available in Asia and is marketed as an anti-emetic (Anti-sickness) drug often prescribed after exposure to chemotherapy. Chemotherapy exposure can often induce nausea and/or vomiting.

The study only involves the one drug, referred to as SENS-218 in this study. The purpose of the study is to support the development of use of SENS-218 in non-Asian population.

The key objective of this study is to identify the pharmacokinetic (PK) parameters of the drug in healthy Caucasian population. The PK refers to what the body does to the body, for example, how quickly the drug is absorbed into the blood stream.

The population who are eligible to take part in the study are healthy male and female, non-smoking volunteers, aged between 18 and 50 years, as determined by screening tests at Simbec.

Participation in the trial will last for about 3 weeks (from first screening visit to final end of study visit).

Study Overview

• Status: Completed
• Conditions: Inner Ear Diseases
• Intervention / Treatment: Drug: SENS-218

Detailed Description

This study consists of a screening visit, 1 treatment period and a post study visit.

These are outlined below:

Screening visit ( Day -14 to Day -1)

- Ensure subjects are eligible for the study.

Treatment period 1 -If all screening assessments are satisfactory, subjects will be invited to attend Simbec to take part in the study. The treatment period consists of 2 overnight stays (Day -1 until the morning of Day 2). One return visit is required at the 48 hour point post dose on Day 3.

Post study visit

-Subjects will be asked to attend Simbec 5-7 days after administration of the last dose for a post study visit. If you are withdrawn from the study, you will still be asked to attend for an end of study assessment.

Subjects may be asked to return again if we need to follow you up.

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Healthy Caucasian males and females (non-pregnant/non-lactating) between 18 and 50 years of age.
2. Female subject of child bearing potential with a negative pregnancy test at the screening visit and willing to use 2 effective methods of contraception, from first dose until 3 months afterwards (i.e., until 3 months after taking IMP).

3. Female subject of non-child bearing potential with with negative pregnancy test at the screening visit.

   For the purposes of this study, this is defined as the subject being amenorrheic for at least 12 consecutive months or at least 4 months post-surgical sterilisation (including bilateral fallopian tube ligation or bilateral oophorectomy with or without hysterectomy) and levels of follicle stimulating hormone (FSH) falling within the respective pathology reference range. In the event a subject's menopause status has been clearly established (for example, the subject indicates she has been amenorrheic for 10 years), but FSH levels are not consistent with a post-menopausal condition, determination of subject eligibility will be at the discretion of the Investigator following consultation with the Sponsor's Responsible Physician.

4. Male subject willing to use 2 effective methods of contraception, (unless anatomically sterile) from first dose until 3 months afterwards (i.e., until 3 months after taking IMP).
5. Subject with a body mass index (BMI) of 18-30 kg/m2. BMI = body weight (kg)/height (m)2.
6. Subject with no clinically significant abnormal serum biochemistry, haematology and urine examination values within 14 days of the first dose.
7. Subject with a negative urinary drugs of abuse screen, determined within 14 days of the first dose (a positive alcohol result may be repeated at the discretion of the Investigator).
8. Subject with negative human immunodeficiency virus (HIV), hepatitis B surface antigen (Hep B) and hepatitis C virus antibody (Hep C) results.
9. Subject with no clinically significant abnormalities in 12-lead electrocardiogram (ECG) determined within 14 days of the first dose.
10. Subject with no clinically significant abnormalities in blood pressure or pulse determined within 14 days of the first dose.
11. Subject is a non-smoker or ex-smoker who has not smoked in the last 3 months (determined by urine cotinine < 500 ng/mL at screening visit).
12. Subject is available to complete the study (including all follow-up visits) and comply with study restrictions.
13. Subject satisfies a medical examiner about their fitness to participate in the study.
14. Subject provides written informed consent to participate in the study.

Exclusion Criteria:

1. Subject with a clinically significant history of gastrointestinal disorder likely to influence drug absorption.
2. Subject in receipt of regular medication (with the exception of contraception) within 14 days of the first dose that may have an impact on the safety and objectives of the study (Investigator's discretion).
3. Subject with evidence of renal, hepatic, central nervous system, respiratory, cardiovascular or metabolic dysfunction.
4. Subjects with any renal (serum creatinine (CREAT) level > 1.5 fold above the upper limit of normal (ULN)) or liver insufficiency (alkaline phosphatase (ALP) level > 1.2 fold above ULN, gamma glutamyl transferase (GGT), aspartate transaminase (AST), or alanine transaminase (ALT) level > 2.5 fold above ULN, and total bilirubin (BIL-T) level > 1.5 fold above ULN).
5. Subject with history of, or family history (immediate relative) of, long QT syndrome or Torsade de Pointes or symptomatic bradycardia.
6. Subject with clinically significant history of previous allergy / sensitivity to SENS-218 or its excipients or other 5-hydroxytryptophan3 (5-HT3) receptor antagonists.
7. Subject with a clinically significant history of drug or alcohol abuse.
8. Subject with inability to communicate well with the Investigator (i.e., language problem, poor mental development or impaired cerebral function).
9. Subject participation in a New Chemical Entity clinical study within the previous 4 months or a marketed drug clinical study within the previous 3 months. (N.B. washout period between studies is defined as the period of time elapsed between the last dose of the previous study and the first dose of the next study).
10. Subject donated 450 mL or more blood within the previous 3 months

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: SENS-218; 2 x 10 mg administered once on Day 1.	Drug: SENS-218; Oral Administration

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Cmax - Max plasma concentration of SENS-218 in healthy adults	0 to 48 hours.
Tmax -Time taken to reach Cmax for SENS-218 in healthy adults	0 to 48 hours.
kel - elimination rate constant of SENS-218 in healthy adults	0 to 48 hours.
t1/2 - Terminal Elimination half life of SENS-218 in healthy adults	0 to 48 hours
AUC0-t - area under the concentration-time curve (AUC) from the time of dosing to last measurable concentration of SENS-218 in healthy adults.	0 to 48 hours
AUC0-inf - the AUC extrapolated to infinity of SENS-218 in healthy	0 to 48 hours
CL/F - clearance, calculated as dose/AUC0-inf of SENS-218 in healthy adults.	0 to 48 hours
MRT - Mean residence time of SENS-218 in healthy adults	0 to 48 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
12-lead ECGs	12-lead ECG assessments: Heart rate, PR interval, QRS width, QT interval and QT interval corrected using Bazett's formula (QTcB).	Day 1 until post study (5 to 7 days following IMP administration)
Vitals signs	Vital signs assessments: Systolic/diastolic blood pressure and pulse rate and oral body temperature. corrected using Bazett's formula (QTcB).	Day 1 until post study (5 to 7 days following IMP administration)
Physical examination		Day 1 until post study (5 to 7 days following IMP administration)

Collaborators and Investigators

• Sponsor: Simbec Research
• Collaborators: Sensorion SA

Study record dates

Study Major Dates

• Study Start: February 1, 2016
• Primary Completion (Actual): March 1, 2016
• Study Completion (Actual): March 1, 2016

Study Registration Dates

• First Submitted: April 25, 2016
• First Submitted That Met QC Criteria: May 11, 2016
• First Posted (Estimate): May 16, 2016

Study Record Updates

• Last Update Posted (Estimate): May 16, 2016
• Last Update Submitted That Met QC Criteria: May 11, 2016
• Last Verified: May 1, 2016

More Information

Terms related to this study

• Keywords: Pharmacokinetics; Healthy Volunteer Study
• Additional Relevant MeSH Terms: Otorhinolaryngologic Diseases; Otitis; Ear Diseases; Labyrinthitis; Labyrinth Diseases
• Other Study ID Numbers: RD 716/33020

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED