Comparison of plasma concentration of rasagiline in different doses with genetic variations and smoking in healthy volunteers
| ISRCTN | ISRCTN68198254 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN68198254 |
| Secondary identifying numbers | N/A |
- Submission date
- 10/05/2016
- Registration date
- 18/05/2016
- Last edited
- 09/07/2024
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Nervous System Diseases
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)
Contact information
Public
Department of Pharmacology
CMH Lahore Medical College & Dental College
Lahore
54810
Pakistan
 ORCID ID |
0000-0002-8161-9731 |
|---|
Scientific
Department of Pharmacology
University of Health Sciences Lahore
Khayaban-e-Jamia, 54000
Lahore
54000
Pakistan
Study information
| Study design | Comparative, Interventional, single oral dose, pharmacokinetic study |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Purposive sampling |
| Study setting(s) | Community |
| Study type | Treatment |
| Scientific title | Rasagiline Pharmacokinetics in CYP1A2 variant healthy smokers and non-smokers in different doses |
| 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(s) | 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 |
| 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 |
| Pharmaceutical study type(s) | Not Applicable |
| Phase | Phase I/II |
| Drug / device / biological / vaccine name(s) | Rasagiline |
| Primary outcome measure | 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 study start date | 01/06/2016 |
| Overall study end date | 31/12/2017 |
Eligibility
| Participant type(s) | Healthy volunteer |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Sex | Both |
| Target number of participants | 108 healthy volunteers |
| Total final enrolment | 108 |
| 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 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
Study participating centre
Lahore
54000
Pakistan
Sponsor information
University/education
Khayaban-e-Jamia
Lahore
54000
Pakistan
| Phone | +92 42 92313049 |
|---|---|
| info@uhs.edu.pk | |
"ROR" |
https://ror.org/00gt6pp04 |
Funders
Funder type
Other
No information available
Results and Publications
| Intention to publish date | 31/12/2018 |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Not provided at time of registration |
| Publication and dissemination plan | To be confirmed at a later date |
| IPD sharing plan | Not provided at time of registration |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Protocol file | 09/08/2022 | No | No | ||
| Results article | 26/01/2022 | 09/07/2024 | Yes | No |
Additional files
Editorial Notes
09/07/2024: Publication reference and total final enrolment added.
09/08/2022: Uploaded protocol (not peer-reviewed) as an additional file.
