Clinical trial NCT02548806: Phase 1 PK, Bioavailability, Safety Study of Clonidine MBT w Catapres in Healthy Volunteers
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Keywords: Clonidine
Lead sponsor: Valerio Therapeutics
Sponsor class: INDUSTRY
Collaborators: name: Simbec Research
First posted: 2015-09-14
Enrollment: 36
Sex: ALL
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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.

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.

Eligibility 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)

Primary outcomes:
measure: Dose proportionality of two strengths of clonidine MBT (50μg and 100 μg) as assessed by Non-compartmental pharmacokinetic analysis (Area Under the Curve)
timeFrame: 3 Months
measure: Bioavailability of clonidine from Clonidine MBT 50 μg and 100 μg with that from oral clonidine hydrochloride 100 μg tablets. (Area Under the Curve)
timeFrame: 3 Months
Secondary outcomes:
measure: General safety information (adverse events, (AEs), 12-lead electrocardiogram (ECG) and vital signs), during the study period.
timeFrame: 3 Months
Other outcomes:
Locations:
city: Merthyr Tydfil
country: United Kingdom
facility: Simbec Research Limited
Study officials:
affiliation: Simbec Research
name: Girish Sharma, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.