Phase 1 PK, Bioavailability, Safety Study of Clonidine MBT w Catapres in Healthy Volunteers

Randomised Single Dose 3 Way Crossover Single Blind Study to Evaluate the Pharmacokinetic Dose Proportionality, Compare the Bioavailability and Safety of Clonidine Mucoadhesive Buccal Tablets (MBT) With Catapres in Normal Healthy Volunteers

The purpose of this study is to determine the pharmacokinetic dose proportionality of 50 μg and 100 μg Clonidine and comparative bioavailability of clonidine with that from the Reference drug, Catapres® 100 μg oral tablets following single dose administration in healthy subjects.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: Clonidine MBT 50µg; Drug: Clonidine MBT 100µg; Drug: Catapres 100μg

Detailed Description

A single blind, randomised, 3-period, 3-sequence single-dose crossover study to determine the pharmacokinetic dose proportionality of Clonidine MBT 50 μg and Clonidine MBT 100 μg and comparative bioavailability of clonidine from the Reference drug, Catapres® 100 μg oral tablets following single dose administration in healthy male and female subjects.

36 subjects will be randomised for 30 to complete the study. The study will comprise of 3 Treatment Periods (1, 2 and 3) and a post study follow up (7 - 12 days after the last dose). Study drug will be administered on the morning of Day 1. Pharmacokinetic (PK) blood samples will be collected for each of three treatment periods. Safety will be evaluated at specified times throughout the study. There will be at least 7 days between dose administrations.

• Study Type: Interventional
• Enrollment (Actual): 36
• Phase: Phase 1

Contacts and Locations

Study Locations

• United Kingdom
  • Merthyr Tydfil, United Kingdom, CF48 4DR
    • Simbec Research Limited

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Main Inclusion Criteria:

• Healthy males or females (non-pregnant/non-lactating) aged 18 - 50 years.
• A Body Mass Index (BMI) of 18-30.
• No clinically significant abnormal serum biochemistry, haematology and urine examination values.
• A negative urinary drugs of abuse screen.
• Negative HIV and Hepatitis B and C results.
• No clinically significant abnormalities in 12-lead electrocardiogram (ECG).
• No clinically significant abnormalities in blood pressure or pulse.
• No allergy or sensitivity to clonidine or any of its excipients.
• No allergy to milk or milk derivatives.
• Subjects must provide written informed consent to participate in the study

Main Exclusion Criteria:

• Current or past medical condition that might significantly affect the pharmacokinetic or
• pharmacodynamic response to clonidine.
• Participation in a New Chemical Entity clinical study within the previous 3 months or a marketed drug clinical study within the previous 30 days.
• Pathological condition of the oral cavity that would affect administration via the buccal route.
• Raynaud's disease or other peripheral vascular disease.
• Receipt of regular medication within 14 days of the first dose that may have an impact on the safety and objectives of the study (at the Investigator's discretion).
• Evidence of renal, hepatic, central nervous system, respiratory, cardiovascular or metabolic dysfunction.
• Symptomatic postural hypotension evident on screening
• History or evidence of Suicidal Ideation and/or behaviour as determined by using Columbia-Suicide Severity Rating Scale (C-SSRS)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Single

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Clonidine MBT 50µg; Each subject will receive the following treatments in random order over 3 Treatment Periods (1 treatment/period): Clonidine MBT 50µg single dose, Clonidine MBT 100μg single dose ,a single-dose of reference catapres 100μg tablets.	Drug: Clonidine MBT 50µg; Clonidine MBT 50µg, single dose; Other Names: Clonidine Lauriad
Experimental: Clonidine MBT 100µg; Each subject will receive the following treatments in random order over 3 Treatment Periods (1 treatment/period): Clonidine MBT 50μg single dose, Clonidine MBT 100µg single dose ,a single-dose of reference catapres 100μg tablets..	Drug: Clonidine MBT 100µg; Clonidine MBT 100µg, single dose; Other Names: Clonidine Lauriad
Active Comparator: Catapres 100μg; Each subject will receive the following treatments in random order over 3 Treatment Periods (1 treatment/period): Clonidine MBT 50μg single dose, Clonidine MBT 100μg single dose ,a single-dose of reference catapres 100μg tablets.	Drug: Catapres 100μg; Catapres tablet 100μg, single dose; Other Names: Catapres

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Dose proportionality of two strengths of clonidine MBT (50μg and 100 μg) as assessed by Non-compartmental pharmacokinetic analysis (Area Under the Curve)	To evaluate dose proportionality of two strengths (50 μg and 100 μg) of Clonidine MBT, by using Area Under the Curve (AUC)	3 Months
Bioavailability of clonidine from Clonidine MBT 50 μg and 100 μg with that from oral clonidine hydrochloride 100 μg tablets. (Area Under the Curve)	To compare the bioavailability of clonidine from Clonidine MBT® 50 μg and 100 μg with that from oral clonidine hydrochloride 100 μg tablets, by using Area Under the Curve (AUC)	3 Months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
General safety information (adverse events, (AEs), 12-lead electrocardiogram (ECG) and vital signs), during the study period.	Number of Participants With Treatment-Related Adverse Events as Assessed by Common Toxicity Criteria for Adverse Effects (CTCAE v4.0), 12-lead electrocardiogram (ECG) and vital signs	3 Months

Collaborators and Investigators

• Sponsor: Onxeo
• Collaborators: Simbec Research
• Investigators: Principal Investigator: Girish Sharma, MD, Simbec Research

Publications and helpful links

General Publications

• Vasseur B, Dufour A, Houdas L, Goodwin H, Harries K, Emul NY, Hutchings S. Comparison of the Systemic and Local Pharmacokinetics of Clonidine Mucoadhesive Buccal Tablets with Reference Clonidine Oral Tablets in Healthy Volunteers: An Open-Label Randomised Cross-Over Trial. Adv Ther. 2017 Aug;34(8):2022-2032. doi: 10.1007/s12325-017-0585-9. Epub 2017 Jul 19.

Study record dates

Study Major Dates

• Study Start: September 1, 2015
• Primary Completion (Actual): December 1, 2015
• Study Completion (Actual): April 1, 2016

Study Registration Dates

• First Submitted: September 2, 2015
• First Submitted That Met QC Criteria: September 10, 2015
• First Posted (Estimate): September 14, 2015

Study Record Updates

• Last Update Posted (Estimate): April 18, 2016
• Last Update Submitted That Met QC Criteria: April 15, 2016
• Last Verified: April 1, 2016

More Information

Terms related to this study

• Keywords: Clonidine
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Antihypertensive Agents; Autonomic Agents; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Adrenergic alpha-2 Receptor Agonists; Adrenergic alpha-Agonists; Adrenergic Agonists; Sympatholytics; Clonidine
• Other Study ID Numbers: OX2015/28/02

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: presentation at ESMO congress