Healthy
Conditions
Keywords
10 mg, KADIAN capsules, 20 mg, fed conditions, bioequivalence
Brief summary
The objective of this single-dose, open-label, randomized, two-treatment, two-period crossover study was to compare the relative bioavailability of a test formulation of KADIAN (2 x 10 mg) capsules manufactured by Alpharma Inc. to an equivalent oral dose of the commercially available reference product, KADIAN (1 x 20 mg)capsules manufactured by Alpharma Branded Products Inc.. Following an overnight fast of at least 10 hours, subjects consumed a standard high-calorie, high-fat breakfast meal that began 30 minutes prior to each dose.
Interventions
2 x 10 mg, single-dose capsule
1 x 20 mg, single-dose capsule
Sponsors
Actavis Inc.
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
* Subject must be a male or non-pregnant, non-breast-feeding female. * Subject must be between 18 and 55 years of age (inclusive). * Subject's Body Mass Index (BMI) must be between 18 and 30 kg/m2 (inclusive), and subject must weigh a minimum of 50 kg (110 lbs). * Female subjects - not surgically sterile or at least two years postmenopausal - must agree to utilize one of the following forms of contraception, if sexually active with a male partner, at least from screening through completion of the study. Approved forms of contraception are abstinence, hormonal (oral, implant, transdermal or injection) in use at least 3 consecutive months prior to first dose of study medication, double barrier (condom with spermicide and diaphragm with spermicide), intra-uterine device (IUD), or vasectomized partner (6 months minimum since vasectomy). * Subject must voluntarily consent to participate in this study and provide their written informed consent prior to completion of any study-specific procedures. * Subject is willing and able to consume the entire high-calorie, high-fat breakfast meal in the designated timeframe required during each study period. * Subject is willing and able to remain in the study unit for the entire duration of each confinement period and return to the study site for all outpatient visits.
Exclusion criteria
* History or presence of clinically significant cardiovascular, pulmonary, hepatic, renal, hematologic, gastrointestinal, endocrine, immunologic, dermatologic, neurologic, oncologic or psychiatric disease or any other condition which, in the opinion of the Investigator would jeopardize the safety of the subject or the validity of the study results. * Has a clinically significant abnormal finding on the physical exam, medical history, ECG or clinical laboratory results at screening. * History or presence of allergic or adverse response to the study drug or related drugs. * Has been on a significantly abnormal diet during the four weeks preceding the first dose of study medication. * Has donated blood or plasma within 30 days prior to the first dose of study medication. * Has participated in another clinical trial within 30 days prior to first dose of study medication. * Has used any over-the-counter (OTC) medication including nutritional supplements, within 7 days prior to the first dose of study medication. * Has used any prescription medication, except hormonal contraceptive or hormonal replacement therapy, within 14 days prior to the first dose of study medication. * Has been treated with any known enzyme altering drugs such as barbiturates, phenothiazines, cimetidine, carbamazepine, etc., within 30 days prior to the first dose of study medication. * Has smoked or used tobacco products within 60 days prior to the first dose of study medication. * Has a history of treatment for substance abuse (including alcohol) in the past 5 years. * Is a female with a positive pregnancy test result. * Has a positive urine screen for drugs of abuse (amphetamines, barbiturates, benzodiazepines, cocaine, cannabinoids, opiates). * Has had a positive test for, or has been treated for Hepatitis B, Hepatitis C or HIV.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Maximum Plasma Morphine Concentration | 0 (predose), and 2,4,6,6.5,7,7.5,8,8.5,9,9.5,10,12,18,24,30,36,48 hrs |
Secondary
| Measure | Time frame |
|---|---|
| Time of Maximum Plasma Morphine Concentration | 0 (predose), and 2,4,6,6.5,7,7.5,8,8.5,9,9.5,10,12,18,24,30,36,48 hrs |
| Area Under the Curve to the Last Measurable Time Point for Plasma Morphine | 0 (predose), and 2,4,6,6.5,7,7.5,8,8.5,9,9.5,10,12,18,24,30,36,48 hrs |
| Area Under the Curve to Infinity for Plasma Morphine | 0 (predose), and 2,4,6,6.5,7,7.5,8,8.5,9,9.5,10,12,18,24,36,48 hrs |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Period 1: Treatment Aor B Treatment A (test product) followed by Treatment B (reference product) | 18 |
| Period 2: Treatment A or B Treatment B (reference product) followed by Treatment A (test product) | 18 |
| Total | 36 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 0 | 1 |
| Overall Study | Withdrawal by Subject | 1 | 0 |
Baseline characteristics
| Characteristic | Period 1: Treatment Aor B | Period 2: Treatment A or B | 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 | 18 Participants | 18 Participants | 36 Participants |
| Age Continuous | 36 years STANDARD_DEVIATION 12 | 29 years STANDARD_DEVIATION 10 | 33 years STANDARD_DEVIATION 12 |
| Region of Enrollment United States | 18 participants | 18 participants | 36 participants |
| Sex: Female, Male Female | 7 Participants | 5 Participants | 12 Participants |
| Sex: Female, Male Male | 11 Participants | 13 Participants | 24 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 4 / — | 6 / — |
| serious Total, serious adverse events | 0 / 0 | 0 / 0 |
Outcome results
Primary
Maximum Plasma Morphine Concentration
Time frame: 0 (predose), and 2,4,6,6.5,7,7.5,8,8.5,9,9.5,10,12,18,24,30,36,48 hrs
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| KADIAN (2 x 10mg) Capsules | Maximum Plasma Morphine Concentration | 4.60 ng/mL | Standard Deviation 1.82 |
| KADIAN 20mg Capsules | Maximum Plasma Morphine Concentration | 4.29 ng/mL | Standard Deviation 2.13 |
90% CI: [100.1, 120.8]ANOVA
Secondary
Area Under the Curve to Infinity for Plasma Morphine
Time frame: 0 (predose), and 2,4,6,6.5,7,7.5,8,8.5,9,9.5,10,12,18,24,36,48 hrs
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| KADIAN (2 x 10mg) Capsules | Area Under the Curve to Infinity for Plasma Morphine | 90.09 hr*ng/mL | Standard Deviation 16.18 |
| KADIAN 20mg Capsules | Area Under the Curve to Infinity for Plasma Morphine | 92.43 hr*ng/mL | Standard Deviation 23.46 |
90% CI: [92.3, 100.97]ANOVA
Secondary
Area Under the Curve to the Last Measurable Time Point for Plasma Morphine
Time frame: 0 (predose), and 2,4,6,6.5,7,7.5,8,8.5,9,9.5,10,12,18,24,30,36,48 hrs
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| KADIAN (2 x 10mg) Capsules | Area Under the Curve to the Last Measurable Time Point for Plasma Morphine | 76.44 hr*ng/mL | Standard Deviation 16.12 |
| KADIAN 20mg Capsules | Area Under the Curve to the Last Measurable Time Point for Plasma Morphine | 76.33 hr*ng/mL | Standard Deviation 19.24 |
90% CI: [96.96, 105]ANOVA
Secondary
Time of Maximum Plasma Morphine Concentration
Time frame: 0 (predose), and 2,4,6,6.5,7,7.5,8,8.5,9,9.5,10,12,18,24,30,36,48 hrs
| Arm | Measure | Value (MEDIAN) | Dispersion |
|---|---|---|---|
| KADIAN (2 x 10mg) Capsules | Time of Maximum Plasma Morphine Concentration | 12.00 Hr | Full Range 3.83 |
| KADIAN 20mg Capsules | Time of Maximum Plasma Morphine Concentration | 12.00 Hr | Full Range 5.17 |