Teriflunomide Elimination, Healthy Volunteers
Conditions
Keywords
teriflunomide, colestipol hcl
Brief summary
Primary Objective To determine if colestipol hydrochloride tablets can accelerate the elimination of teriflunomide. Teriflunomide will be administered for 14 days followed by colestipol dosing of 11 days. Total duration of the study is 40 days. Secondary Objectives To collect information on the pattern of side effects with use of colestipol hydrochloride after teriflunomide administration and to determine the best duration of therapy needed for adequate elimination
Detailed description
participants will be followed for 40 days to allow for time to administer a loading dose of teriflunomide and observe the elimination of that drug using colestipol hcl.
Interventions
DRUGteriflunomide
DRUGColestipol
Sponsors
Genzyme, a Sanofi Company
University of South Florida
Derrick Scott Robertson
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 45 Years
Healthy volunteers
Yes
Inclusion criteria
To be eligible for entry into this study, candidates must meet all of the following eligibility criteria at the time of the baseline visit: 1. Participants having provided informed consent with signature on informed consent form: the informed consent process should be complete with full discussion of all requirements and possible risks. 2. Healthy volunteer\* 3. Aged 18-45 years, inclusive 4. Body Mass Index of 18-29 kg/m2 (body weight of 40-85 kg for women and 50-95 kg for men) \*Healthy volunteer is defined as free of concomitant medications and use of either treatment, as deemed by the Investigator, is not contraindicated with any past medical history of the participant.
Exclusion criteria
1. Current smoker or past history as smoker. 2. Unable to provide informed consent to participate in the study Such as a mental condition rendering the participant unable to understand the nature, scope, and possible consequences of the study 3. Participant unlikely to comply with protocol as determined by Investigator, eg, uncooperative attitude, inability to return for follow-up visits 4. Clinically relevant cardiovascular, hepatic, neurological, endocrine, or other major systemic disease making implementation of the protocol or interpretation of the study results difficult or that would put the participant at risk by participating in the study 5. Persistent significant or severe infection, either acute or chronic 6. Recent history of drug or alcohol abuse within that past 6 months (participants will be asked to refrain from alcohol and drug use during the course of the study) 7. Participant is the Investigator or any Sub-investigator, research assistant, pharmacist, study coordinator, other staff or relative thereof, directly involved in the conduct of the protocol 8. Prior use of any investigational drug in the preceding 6 months 9. Liver function impairment or persisting elevations (confirmed by retest) of alanine aminotransferase (ALT), aspartate aminotransferase (AST), or direct bilirubin greater than 2x the upper limit of normal range (ULN). 10. Pregnant or breast-feeding women or those who plan to become pregnant during the study 11. Women of childbearing potential not protected by effective contraceptive method of birth control and/or who are unwilling or unable to be tested for pregnancy. 12. Participants wishing to parent children (be a partner in the conception of a child) during the course of the trial. 13. Participants with significantly impaired bone marrow function or significant anemia, leukopenia, or thrombocytopenia (confirmed by retest): * Hematocrit \< 35% and/or * Absolute white blood cell count \< 3000 cells/mm3 (μL) and/or * Platelet count \< 150 000 cells/mm3 (μL) and/or- Absolute neutrophil ≤ 1500 cells/mm3 (μL) 14. Any known history of severe preexisting constipation 15. History of swallowing disorder or difficulty swallowing
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Primary Outcome Measures: Teriflunomide Concentrations at Day 28 | 28 days after the start in the study | After receiving 14 days of teriflunomide, participants will take 11 days of colestipol to wash out the teriflunomide (measuring the levels of teriflunomide in the blood at each visit) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Secondary Outcome Measure: Mean Percentage Change of Serum Teriflunomide Levels Percentage Change of Teriflunomide Concentrations at Day 8, Day 14, Day 26 ad Day 36 Following Administration of Colestipol Hydrochloride Tablets. | duration of study about 50 days | The last blood draw will be about 50 days from the start of the study |
Countries
United States
Participant flow
Recruitment details
Enrollment occurred from March 2015 through May 2016 at the USF Carol and Frank Morsani Center.
Pre-assignment details
Participants were healthy individuals with no significant health history or concomitant medication use.
Participants by arm
| Arm | Count |
|---|---|
| Teriflunomide Elimination With Colestipol teriflunomide
Colestipol | 14 |
| Total | 14 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 1 |
| Overall Study | Lost to Follow-up | 2 |
Baseline characteristics
| Characteristic | Teriflunomide Elimination With Colestipol |
|---|---|
| Age, Continuous | 24.5 years STANDARD_DEVIATION 7.9 |
| BMI | 23.9 kg/m^2 STANDARD_DEVIATION 2.7 |
| Race/Ethnicity, Customized Asian | 1 Participants |
| Race/Ethnicity, Customized Black | 2 Participants |
| Race/Ethnicity, Customized Caucasian | 7 Participants |
| Race/Ethnicity, Customized Hispanic | 4 Participants |
| Sex: Female, Male Female | 4 Participants |
| Sex: Female, Male Male | 10 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 12 / 14 |
| serious Total, serious adverse events | 0 / 14 |
Outcome results
Primary
Primary Outcome Measures: Teriflunomide Concentrations at Day 28
After receiving 14 days of teriflunomide, participants will take 11 days of colestipol to wash out the teriflunomide (measuring the levels of teriflunomide in the blood at each visit)
Time frame: 28 days after the start in the study
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Teriflunomide Elimination With Colestipol | Primary Outcome Measures: Teriflunomide Concentrations at Day 28 | 9.36 teriflunomide level (mcg/ml) | Standard Deviation 4.26 |
Secondary
Secondary Outcome Measure: Mean Percentage Change of Serum Teriflunomide Levels Percentage Change of Teriflunomide Concentrations at Day 8, Day 14, Day 26 ad Day 36 Following Administration of Colestipol Hydrochloride Tablets.
The last blood draw will be about 50 days from the start of the study
Time frame: duration of study about 50 days
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Teriflunomide Elimination With Colestipol | Secondary Outcome Measure: Mean Percentage Change of Serum Teriflunomide Levels Percentage Change of Teriflunomide Concentrations at Day 8, Day 14, Day 26 ad Day 36 Following Administration of Colestipol Hydrochloride Tablets. | 8 days after colestipol hcl administered | -56.4 percentage change in teriflunomide level | Standard Deviation 21.9 |
| Teriflunomide Elimination With Colestipol | Secondary Outcome Measure: Mean Percentage Change of Serum Teriflunomide Levels Percentage Change of Teriflunomide Concentrations at Day 8, Day 14, Day 26 ad Day 36 Following Administration of Colestipol Hydrochloride Tablets. | 14 days after colestipol hcl administered | -74.9 percentage change in teriflunomide level | Standard Deviation 27 |
| Teriflunomide Elimination With Colestipol | Secondary Outcome Measure: Mean Percentage Change of Serum Teriflunomide Levels Percentage Change of Teriflunomide Concentrations at Day 8, Day 14, Day 26 ad Day 36 Following Administration of Colestipol Hydrochloride Tablets. | 26 days after colestipol hcl administered | -94.9 percentage change in teriflunomide level | Standard Deviation 6.3 |
| Teriflunomide Elimination With Colestipol | Secondary Outcome Measure: Mean Percentage Change of Serum Teriflunomide Levels Percentage Change of Teriflunomide Concentrations at Day 8, Day 14, Day 26 ad Day 36 Following Administration of Colestipol Hydrochloride Tablets. | 36 days after colestipol hcl administered | -96.9 percentage change in teriflunomide level | Standard Deviation 3.7 |