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

• ClinicalTrials.gov Identifier: NCT02548806
• Recruitment Status: Completed
• First Posted: September 14, 2015
• Last Update Posted: April 18, 2016
• Sponsor: Onxeo
• Collaborator: Simbec Research
• Information provided by (Responsible Party): Onxeo

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Healthy	Drug: Clonidine MBT 50µg; Drug: Clonidine MBT 100µg; Drug: Catapres 100μg	Phase 1

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 36 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Single (Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: 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
• Study Start Date: September 2015
• Actual Primary Completion Date: December 2015
• Actual Study Completion Date: April 2016

Arms and Interventions

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 Name: 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 Name: 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 Name: Catapres

Outcome Measures

Primary Outcome Measures :

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

Secondary Outcome Measures :

1. General safety information (adverse events, (AEs), 12-lead electrocardiogram (ECG) and vital signs), during the study period. [ Time Frame: 3 Months ]
   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

Eligibility Criteria

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

Criteria

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)

Contacts and Locations

Locations

United Kingdom

Simbec Research Limited

Merthyr Tydfil, United Kingdom, CF48 4DR

Sponsors and Collaborators

Onxeo

Simbec Research

Investigators

• Principal Investigator: Girish Sharma, MD; Simbec Research

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: Onxeo
• ClinicalTrials.gov Identifier: NCT02548806
• Other Study ID Numbers: OX2015/28/02
• First Posted: September 14, 2015
• Last Update Posted: April 18, 2016
• Last Verified: April 2016

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: presentation at ESMO congress

Keywords provided by Onxeo:

Clonidine

Additional relevant MeSH terms:

Clonidine; Analgesics; Sensory System Agents; Peripheral Nervous System Agents; Physiological Effects of Drugs; Antihypertensive Agents; Sympatholytics; Autonomic Agents; Adrenergic alpha-2 Receptor Agonists; Adrenergic alpha-Agonists; Adrenergic Agonists; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action