Healthy
Conditions
Keywords
Healthy, Bioequivalence, Pharmacokinetics
Brief summary
This is an open label randomized single dose two-way crossover study to compare the bioavailability of a single oral dose of quinine sulfate 648 mg(2 x 324 mg) when mixed with 120 ml of chocolate pudding relative to the same dose given as two intact capsules.
Detailed description
Prior studies have shown that intact quinine sulfate capsules can be taken without regard for food. This is an open label randomized single dose two-way crossover study to compare the bioavailability of a single oral dose of quinine sulfate 648mg(2 x 324 mg capsules) when opened and mixed with 120 ml of chocolate pudding relative to the same dose given as two intact capsules. Eighteen healthy adult subjects will be enrolled. Following a fast of at least 10 hours subjects will be randomized to receive either 648 mg of quinine sulfate as the intact capsules or opened mixed in 120ml of chocolate pudding. Following a washout period of at least 7 days all subjects will be given the alternate dose under similar conditions. Following each dose, blood samples will be collected at times sufficient to determine the difference in bioavailability (if any) between the two methods of drug administration. In addition patients will be monitored for any adverse events including Electrocardiogram (EKG) changes (at baseline and 4 hours after each dose).
Interventions
DRUGquinine sulfate
2 x 324 mg capsules (648 mg)
Sponsors
Mutual Pharmaceutical Company, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 50 Years
Healthy volunteers
Yes
Inclusion criteria
* Healthy nonsmoking adults with hemoglobin at least 12 g/dl. Males at least 52 kg, females at least 45kg with body mass index in the normal range, females must be chemically or surgically sterile or postmenopausal (amenorrhea at least 2years)
Exclusion criteria
* Pregnant or lactating * Test positive at screening for human immunodeficiency virus (HIV), hepatitis B surface antigen (HbsAg), or hepatitis C virus (HCV) Recent (1-year) history or evidence of alcoholism or drug abuse History or presence of significant cardiovascular, pulmonary, hepatic, renal, hematological, gastrointestinal, endocrine, immunologic, dermatologic, neurological, or psychiatric disease, myasthenia gravis, optic neuritis or Glucose-6-phosphate dehydrogenase (G6PD) deficiency * Prolonged corrected QT interval(QTc) on Electrocardiogram(EKG) at screening -males \>430 msec, females \>450 msec. PR interval on EKG \>200 msec at screening or prior to dose in either dosing period * Subjects who have used any drugs or substances known to inhibit or induce cytochrome (CYP) P450 enzymes and/or P-glycoprotein (P-gp) within 30 days prior to the first dose and throughout the study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Observed Plasma Concentration (Cmax) | After dosing at time points 0, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 7, 8, 10, 12, 16, 24, 36, and 48 hours | The highest concentration of drug in plasma after a dose. Measured to evaluate the bioequivalence of the two dosing methods |
| Area Under the Concentration Time Curve From Zero to t. (AUC 0-t) | After dosing at time points 0, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 7, 8, 10, 12, 16, 24, 36, and 48 hours | The area under the plasma concentration versus time curve from zero to the last measurable plasma concentration as calculated by the linear trapezoidal method. Calculated to determine whether the 2 methods of administration are bioequivalent. |
| The Area Under the Plasma Concentration Versus Time Curve From Time Zero to Infinity. (AUC Inf) | After dosing at time points 0, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 7, 8, 10, 12, 16, 24, 36, and 48 hours | AUC inf is calculated as the sum of the AUC 0-t plus the ratio of the last measurable plasma concentration to the elimination rate constant.It is calculated to evaluate the bioequivalence of the two dosing methods |
Countries
Canada
Participant flow
Pre-assignment details
Participants were randomized to receive a single dose of quinine 648 mg (2 x 324 mg) either as intact capsules or capsules opened and their contents mixed in 120 mL chocolate pudding after a fast of at least 10 hours. Following a 7 day wash out period, all participants were given the alternate dose under similar conditions.
Participants by arm
| Arm | Count |
|---|---|
| Quinine Alone First After a fast of at least 10 hours, participants received a single dose of quinine 648 mg (2 x 324 mg) as intact capsules. Blood was drawn sufficient to characterize the pharmacokinetics of quinine after this dose. | 9 |
| Quinine With Chocolate Pudding First After a fast of at least 10 hours participants received a single dose of quinine 648 mg (2 x 324 mg) capsules opened and mixed in 120 mL chocolate pudding. Blood was drawn at times sufficient to characterize the pharmacokinetics of quinine after this dose. | 9 |
| Total | 18 |
Baseline characteristics
| Characteristic | Quinine Alone First | Quinine With Chocolate Pudding First | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 9 Participants | 9 Participants | 18 Participants |
| Age Continuous | 35.5 years STANDARD_DEVIATION 8.4 | 35.5 years STANDARD_DEVIATION 8.4 | 35.5 years STANDARD_DEVIATION 8.4 |
| Sex: Female, Male Female | 3 Participants | 3 Participants | 6 Participants |
| Sex: Female, Male Male | 6 Participants | 6 Participants | 12 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 7 / 18 | 10 / 18 |
| serious Total, serious adverse events | 0 / 18 | 0 / 18 |
Outcome results
Primary
Area Under the Concentration Time Curve From Zero to t. (AUC 0-t)
The area under the plasma concentration versus time curve from zero to the last measurable plasma concentration as calculated by the linear trapezoidal method. Calculated to determine whether the 2 methods of administration are bioequivalent.
Time frame: After dosing at time points 0, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 7, 8, 10, 12, 16, 24, 36, and 48 hours
Population: Analysis was performed per protocol
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Quinine Alone | Area Under the Concentration Time Curve From Zero to t. (AUC 0-t) | 555973.3 ng·h/mL | Standard Deviation 15455.81 |
| Quinine With Chocolate Pudding | Area Under the Concentration Time Curve From Zero to t. (AUC 0-t) | 56008.6 ng·h/mL | Standard Deviation 12979.18 |
Primary
Maximum Observed Plasma Concentration (Cmax)
The highest concentration of drug in plasma after a dose. Measured to evaluate the bioequivalence of the two dosing methods
Time frame: After dosing at time points 0, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 7, 8, 10, 12, 16, 24, 36, and 48 hours
Population: Analysis was performed per protocol
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Quinine Alone | Maximum Observed Plasma Concentration (Cmax) | 3291.411 ng per mL | Standard Deviation 658.529 |
| Quinine With Chocolate Pudding | Maximum Observed Plasma Concentration (Cmax) | 3439.867 ng per mL | Standard Deviation 646.818 |
Primary
The Area Under the Plasma Concentration Versus Time Curve From Time Zero to Infinity. (AUC Inf)
AUC inf is calculated as the sum of the AUC 0-t plus the ratio of the last measurable plasma concentration to the elimination rate constant.It is calculated to evaluate the bioequivalence of the two dosing methods
Time frame: After dosing at time points 0, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 7, 8, 10, 12, 16, 24, 36, and 48 hours
Population: Analysis was performed per protocol
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Quinine Alone | The Area Under the Plasma Concentration Versus Time Curve From Time Zero to Infinity. (AUC Inf) | 61887.4 ng-h/ml | Standard Deviation 18880.15 |
| Quinine With Chocolate Pudding | The Area Under the Plasma Concentration Versus Time Curve From Time Zero to Infinity. (AUC Inf) | 60764.9 ng-h/ml | Standard Deviation 14998.61 |