Renal Insufficiency
Conditions
Brief summary
The steady-state pharmacokinetics of Dalfampridine-ER (extended release) 7.5 mg (milligram) tablets in healthy adult volunteers and those with mild and moderate renal impairment, and examine between group comparisons.
Detailed description
Pharmacokinetics in normal, mildly renally impaired, and moderately renally impaired subjects
Interventions
DRUGDalfampridine-ER
2 days of single dose 7.5 mg, 4 days of bid dosing, and a 3 day follow-up
Sponsors
Acorda Therapeutics
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
Yes
Inclusion criteria
* Either gender between the ages of 18 and 75 years * Have a body mass index (BMI) ranging between 18.5 - 35.0 kg/m2, inclusive * Have adequate cognitive function to understand and sign the IRB approved informed consent prior to the performance of any study-specific procedures * Be willing and able to comply with all trial requirements * Fit into one of three 12-subject groups: normal renal function (CrCl \> 80 mL/min), mild renal impairment (CrCl 51-80 mL/min), and moderate renal impairment (CrCl 30-50 mL/min) * Have sufficient venous access to permit blood sample collection * Women of childbearing potential must have a negative β-HCG pregnancy test at the Screening Visit.
Exclusion criteria
* Women who are either pregnant or breastfeeding, and women of childbearing potential (i.e., has not had a hysterectomy or bilateral oophorectomy, or is not at least two years postmenopausal) who are engaged in active heterosexual relations and not using any of the following birth control methods: tubal ligation, implantable contraception device, oral, patch or injectible contraceptive, double barrier method, or sexual activity restricted to a vasectomized partner; * History of seizure(s); * Unstable, acute, or severe (CrCl \< 30 mL/min) renal failure; * Clinically significant abnormal findings on the physical examination, ECG, vital signs, medical history, or clinical laboratory results during screening (other than abnormal renal values); * Any unstable cardiovascular, enterohepatic, respiratory, or immunologic disorder or disease that may substantially affect the pharmacokinetics of Dalfampridine-ER; * Known allergy to pyridine-containing substances, or any of the inactive ingredients of the Dalfampridine-ER tablet (colloidal silicon dioxide, hydroxypropyl methylcellulose, magnesium stearate, microcrystalline cellulose, polyethylene glycol, and titanium dioxide); * Participation in an investigational drug trial 30 days prior to Screening or plans to enroll in an investigational drug trial at any time during this study; * Any medical condition including psychiatric disease that would interfere with the interpretation of the study results or the conduct of the study; * Subject has started a new medication (prescription, vitamins, herbal medications, or other over-the-counter medications), or had a change in their existing medication within 30 days prior to screening; * History of drug or alcohol abuse in the past 2 years, or tests positive for drugs of abuse at Screening; * Donation of blood or blood components within 30 days prior to administration of investigational drug. The Investigator should instruct subjects who participate in this study not to donate blood or blood components during their participation in the study and up to four weeks after the completion of the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Steady State Area Under the Drug Concentration Time Curve From 0 to 12 Hours Post Dose AUC(0-12). | 0 and 1,2,3,4,5,6,8, and 12 hours after the last dose | AUC(0-12) was based on blood samples taken at specified outcome measure time frame for dalfampridine-ER 7.5 mg tablets in healthy adult volunteers and people with mild or moderate renal impairment. |
Secondary
| Measure | Time frame |
|---|---|
| The Maximum Measured Plasma Concentration (Cmax) at Steady State, of Dalfampridine-ER 7.5 mg Tablets in Healthy Adult Volunteers and Those With Mild and Moderate Renal Impairment and Examine Between-group Differences. | 7 days |
| The Steady State Fractional Clearance, Calculated as the Dose / AUC(0-12) (CL/Fss) of Dalfampridine-ER 7.5 mg Tablets in Healthy Adult Volunteers and Those With Mild and Moderate Renal Impairment and Examine Between-group Differences. | 7 days |
Countries
United States
Participant flow
Recruitment details
First subject screened January, 2011. Last subject out August, 2011. Full Service Phase 1 Units.
Participants by arm
| Arm | Count |
|---|---|
| Healthy: Dalfampridine-ER 7.5 mg Dalfampridine-ER 7.5 mg single and steady-state dosing in healthy volunteers
Dalfampridine-ER : 2 days of single dose 7.5 mg, 4 days of bid dosing, and a 3 day follow-up | 13 |
| Mild Renal: Dalfampridine-ER 7.5 mg Dalfampridine-ER 7.5 mg single and steady-state dosing in volunteers with mild renal impairment
Dalfampridine-ER : 2 days of single dose 7.5 mg, 4 days of bid dosing, and a 3 day follow-up | 17 |
| Moderate Renal: Dalfampridine-ER 7.5 mg Dalfampridine-ER 7.5 mg single and steady-state dosing in volunteers with moderate renal impairment
Dalfampridine-ER : 2 days of single dose 7.5 mg, 4 days of bid dosing, and a 3 day follow-up | 12 |
| Total | 42 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Lost to Follow-up | 1 | 0 | 0 |
Baseline characteristics
| Characteristic | Healthy: Dalfampridine-ER 7.5 mg | Mild Renal: Dalfampridine-ER 7.5 mg | Moderate Renal: Dalfampridine-ER 7.5 mg | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 2 Participants | 7 Participants | 10 Participants | 19 Participants |
| Age, Categorical Between 18 and 65 years | 11 Participants | 10 Participants | 2 Participants | 23 Participants |
| Age Continuous | 41.9 years STANDARD_DEVIATION 14.65 | 63.2 years STANDARD_DEVIATION 7.22 | 67.1 years STANDARD_DEVIATION 7.65 | 57.7 years STANDARD_DEVIATION 14.71 |
| Race/Ethnicity, Customized Asian | 0 participants | 4 participants | 2 participants | 6 participants |
| Race/Ethnicity, Customized Black or African American | 1 participants | 2 participants | 2 participants | 5 participants |
| Race/Ethnicity, Customized Other | 1 participants | 0 participants | 0 participants | 1 participants |
| Race/Ethnicity, Customized White | 11 participants | 11 participants | 8 participants | 30 participants |
| Sex: Female, Male Female | 3 Participants | 7 Participants | 4 Participants | 14 Participants |
| Sex: Female, Male Male | 10 Participants | 10 Participants | 8 Participants | 28 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 8 / 13 | 8 / 17 | 4 / 12 |
| serious Total, serious adverse events | 0 / 13 | 0 / 17 | 0 / 12 |
Outcome results
Primary
The Steady State Area Under the Drug Concentration Time Curve From 0 to 12 Hours Post Dose AUC(0-12).
AUC(0-12) was based on blood samples taken at specified outcome measure time frame for dalfampridine-ER 7.5 mg tablets in healthy adult volunteers and people with mild or moderate renal impairment.
Time frame: 0 and 1,2,3,4,5,6,8, and 12 hours after the last dose
Population: Intention to treat (ITT)
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Healthy: Dalfampridine-ER 7.5 mg | The Steady State Area Under the Drug Concentration Time Curve From 0 to 12 Hours Post Dose AUC(0-12). | 157.8 hour*nanogram/milliliter |
| Mild Renal: Dalfampridine-ER 7.5 mg | The Steady State Area Under the Drug Concentration Time Curve From 0 to 12 Hours Post Dose AUC(0-12). | 276.5 hour*nanogram/milliliter |
| Moderate Renal: Dalfampridine-ER 7.5 mg | The Steady State Area Under the Drug Concentration Time Curve From 0 to 12 Hours Post Dose AUC(0-12). | 415.3 hour*nanogram/milliliter |
Secondary
The Maximum Measured Plasma Concentration (Cmax) at Steady State, of Dalfampridine-ER 7.5 mg Tablets in Healthy Adult Volunteers and Those With Mild and Moderate Renal Impairment and Examine Between-group Differences.
Time frame: 7 days
Population: ITT
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Healthy: Dalfampridine-ER 7.5 mg | The Maximum Measured Plasma Concentration (Cmax) at Steady State, of Dalfampridine-ER 7.5 mg Tablets in Healthy Adult Volunteers and Those With Mild and Moderate Renal Impairment and Examine Between-group Differences. | 20.61 nanogram/milliliter |
| Mild Renal: Dalfampridine-ER 7.5 mg | The Maximum Measured Plasma Concentration (Cmax) at Steady State, of Dalfampridine-ER 7.5 mg Tablets in Healthy Adult Volunteers and Those With Mild and Moderate Renal Impairment and Examine Between-group Differences. | 33.92 nanogram/milliliter |
| Moderate Renal: Dalfampridine-ER 7.5 mg | The Maximum Measured Plasma Concentration (Cmax) at Steady State, of Dalfampridine-ER 7.5 mg Tablets in Healthy Adult Volunteers and Those With Mild and Moderate Renal Impairment and Examine Between-group Differences. | 46.69 nanogram/milliliter |
Secondary
The Steady State Fractional Clearance, Calculated as the Dose / AUC(0-12) (CL/Fss) of Dalfampridine-ER 7.5 mg Tablets in Healthy Adult Volunteers and Those With Mild and Moderate Renal Impairment and Examine Between-group Differences.
Time frame: 7 days
Population: ITT
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Healthy: Dalfampridine-ER 7.5 mg | The Steady State Fractional Clearance, Calculated as the Dose / AUC(0-12) (CL/Fss) of Dalfampridine-ER 7.5 mg Tablets in Healthy Adult Volunteers and Those With Mild and Moderate Renal Impairment and Examine Between-group Differences. | 47.54 liter/hour |
| Mild Renal: Dalfampridine-ER 7.5 mg | The Steady State Fractional Clearance, Calculated as the Dose / AUC(0-12) (CL/Fss) of Dalfampridine-ER 7.5 mg Tablets in Healthy Adult Volunteers and Those With Mild and Moderate Renal Impairment and Examine Between-group Differences. | 27.12 liter/hour |
| Moderate Renal: Dalfampridine-ER 7.5 mg | The Steady State Fractional Clearance, Calculated as the Dose / AUC(0-12) (CL/Fss) of Dalfampridine-ER 7.5 mg Tablets in Healthy Adult Volunteers and Those With Mild and Moderate Renal Impairment and Examine Between-group Differences. | 18.06 liter/hour |