Condition category
Nervous System Diseases
Date applied
10/05/2016
Date assigned
18/05/2016
Last edited
17/05/2016
Prospective/Retrospective
Prospectively registered
Overall trial status
Ongoing
Recruitment status
No longer recruiting

Plain English Summary

Background and study aims
Parkinson’s disease (PD) is a chronic condition where nerve cells in a small part of the brain called the substantia nigra become damaged and die. The nerve cells in this region send signals that controls the muscles of the body. Dopamine is the main neurotransmitter produced by these nerve cells. As more of these cells die, the amount of dopamine produced also falls. Over time, the lack of nerve cells and low levels of dopamine affects how well the person affected can control their muscles. The most common symptoms of the condition are slowness of movement, muscle stiffness and shaking (tremors). The condition can have a serious impact on a person’s quality of life (QoL). There are drug treatments that aim to improve QoL but they can have serious side effects for people depending on their genotype (a person’s genetic makeup). Rasagiline is one such drug treatment. It can be taken on its own or in combination with other drugs to ease the symptoms of PD. It is metabolized (broken down) by an enzyme in the liver called CYP 1A2 and is removed from the body through the kidney. CYP 1A2 belongs to the CYP 450 family of enzymes. There are multiple variants (types) of these enzymes; which can vary in different ethnic groups throughout the world. CYP1A2 has three variants (A/A, A/C & C/C). The metabolism of rasagiline is very fast in A/A variants and much slower in the C/C variant group. The present study is aims to observe the rate of oral absorption and metabolism of rasagiline in healthy volunteers.

Who can participate?
Healthy volunteers aged between 18-30.

What does the study involve?
All participants undergo genotyping to determine which variant of the CYP 1A2 enzyme they have ((A/A, A/C or C/C). They are assigned into groups according to genotype and then further split into smokers and non-smokers. All participants are given three doses of rasagiline - 1 mg, 2 mg and 5 mg. Blood samples are taken just after taking the drug and then at 0.25, 0.30, 1, 2, 4, 6, 8, 10,14 and 18 hours after taking the drug. Serum blood levels (the amount of the drug in the blood) are then estimated using a variety of laboratory techniques.

What are the possible benefits and risks of participating?
Not provided at time of registration.

Where is the study run from?
University of Veterinary and Animal Sciences Lahore (Pakistan)

When is the study starting and how long is it expected to run for?
June 2016 to December 2017

Who is funding the study?
Investigator initiated and funded

Who is the main contact?
1. Dr Rabiea Munir (public)
2. Professor Naseem Saud (scientific)

Trial website

Contact information

Type

Public

Primary contact

Dr Rabiea Munir

ORCID ID

http://orcid.org/0000-0002-8161-9731

Contact details

Department of Pharmacology
CMH Lahore Medical College & Dental College
Lahore
54810
Pakistan

Type

Scientific

Additional contact

Prof Naseem Saud

ORCID ID

Contact details

Department of Pharmacology
University of Health Sciences Lahore
Khayaban-e-Jamia
54000
Lahore
54000
Pakistan

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

N/A

Study information

Scientific title

Rasagiline Pharmacokinetics in CYP1A2 variant healthy smokers and non-smokers in different doses

Acronym

Study hypothesis

There is difference in mean pharmacokinetics of rasagiline in A/A, A/C & C/C variants of CYP1A2 smokers & non smokers.

Ethics approval

1. Ethical review committee for Medical and Biomedical research, University of Health Sciences Lahore, Pakistan, 25/03/2016
2. Independent Institutional Ethics Committee, Bioequivalence Study Centre, University of Veterinary and Animal Sciences Lahore, Pakistan, 25/03/2016

Study design

Comparative, Interventional, single oral dose, pharmacokinetic study

Primary study design

Interventional

Secondary study design

Purposive sampling

Trial setting

Community

Trial type

Treatment

Patient information sheet

Condition

Parkinson's disease

Intervention

Healthy volunteers will be recruited and screening for blood, hepatic and renal functions will be performed to fulfill the inclusion criteria in this study.

Genotyping will be carried out for variants of CYP1A2 (A/A, A/C, C/C) till 108 volunteers are identified. All the participants will be sub-grouped into smokers and nonsmokers.

One of three possible doses of rasagiline (1 mg, 2 mg and 5 mg) will be given to equal number of participants in each subgroup and serial blood sampling carried out at 0, 0.25, 0.30, 1, 2, 4, 6, 8, 10,14 and 18 hrs.

Drug extraction, method validation, and HPLC with UV detector will be used to estimate serum drug levels. Pharmacokinetic parameters (Cmax, T Max, AUC, t1/2 , Vd & Cl) will be calculated using the available software by entering plasma concentration time profile. Statistical analysis will be done using 2-way ANOVA to find any significant difference between all the groups.

Intervention type

Drug

Phase

Phase I/II

Drug names

Primary outcome measures

Dose of rasagiline required to ensure effective plasma concentrations to achieve clinical response in participants with CYP1A2 A/A, A/C & C/C variant and smokers measured using pharmacokinetic variables (Cmax, Tmax, AUC, t1/2,Vd & Cl), at (0, 0.25, 0.30, 1,2,4,6, 8, 10 & 14 & 18hrs)

Secondary outcome measures

N/A

Overall trial start date

01/06/2016

Overall trial end date

31/12/2017

Reason abandoned

Eligibility

Participant inclusion criteria

1. Healthy volunteers of both sexes
2. Age between 18 to 30 years
3. Body Mass Index <30 (BMI=weight/height2)
4. Smoking will be defined as present if a participant reports to be smoking at the time of survey either daily or occasionally
5. Non-smoker is a person who does not smoke at all or at the time of survey

Participant type

Healthy volunteer

Age group

Adult

Gender

Both

Target number of participants

108 healthy volunteers

Participant exclusion criteria

1. Volunteers with unstable medical condition or deranged CBC, LFT & RFT
2. Volunteers with history of drug allergies
3. Volunteers who have received any medication which is substrate for CYP1A2
4. Volunteers who have donated blood within 2 months
5. Pregnant women

Recruitment start date

01/06/2016

Recruitment end date

01/10/2016

Locations

Countries of recruitment

Pakistan

Trial participating centre

University of Veterinary and Animal Sciences Lahore
Shaykh Abdul Qadir Jilani Rd
Lahore
54000
Pakistan

Sponsor information

Organisation

University of Health Sciences Lahore

Sponsor details

Khayaban-e-Jamia
Lahore
54000
Pakistan
+92 42 92313049
info@uhs.edu.pk

Sponsor type

University/education

Website

Funders

Funder type

Other

Funder name

Investigator initiated and funded

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

To be confirmed at a later date

Intention to publish date

31/12/2018

Participant level data

Not provided at time of registration

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes