Healthy Volunteers
Conditions
Brief summary
Compare the pharmacokinetic profiles when the contents are emptied into a soft food and orange juice compared to the SPD489 when swallowed as an intact capsule.
Interventions
DRUGLisdexamfetamine Dimesylate
Single dose of a 70 mg capsule on Day 1
Sponsors
Shire
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
1. Age 18-55 years inclusive at the time of consent. The date of signing informed consent is defined as the beginning of the Screening Period. This inclusion criterion will only be assessed at the first screening visit. 2. Willingness to comply with any applicable contraceptive requirements fo the protocol and is: * Male, or * Non pregnant, non lactating female * Females must be at least 90 days post partum or nulliparous 3. Must be considered healthy. Healthy status is defined by absence of evidence of any active or chronic disease following a detailed medical and surgical history, a complete physical examination including vital signs, 12-lead electrocardiogram, hematology, blood chemistry, and urinalysis. 4. An understanding, ability, and willingness to fully comply with study procedures and restrictions 5. Ability to provide written, personally signed, and dated informed consent to participate in the study, in accordance with International Conference on harmonisation Good Clinical Practice Guideline E6 (1996) and applicable regulations, before completing any study related procedures 6. A body mass index between 18.5-30.0kg/m² inclusive. This inclusion criterion will only be assessed at the first screening visit. 7. A hemoglobin value of \>=12.0g/dL at the Screening Visit and on Day -1 of Treatment Period 1. 8. Ability to swallow a dose of investigational product according to the study conditions.
Exclusion criteria
Subjects are excluded from the study if any of the following criteria are met at the Screening Visit or at Day 1 of Treatment Period 1 (if reassessed): 1. Current or recurrent disease (eg, cardiovascular, renal, liver, gastrointestinal, malignancy, or other conditions) that could affect the action, absorption, or disposition of the investigational products, or could affect clinical or laboratory assessments. 2. Current or relevant history of physical or psychiatric illness, any medical disorder that may require treatment or make the subject unlikely to fully comply with the requirements of the study or complete the study, or any condition that presents undue risk from the investigational product or study procedures. 3. Significant illness, as judged by the investigator, within 2 weeks of the first dose of investigational product. 4. History of significant anxiety, tension, or agitation as assessed by the investigator. 5. History of or current diagnosis of glaucoma. 6. History of a seizure disorder (other than infantile febrile seizures), any tic disorder, or a current diagnosis and/or known family history of Tourette's Disorder. 7. History or presence of known structural cardiac abnormalities, syncope, cardiac conduction problems, exercise-related cardiac events, or clinically significant bradycardia. 8. History of symptomatic cardiovascular disease, advanced arteriosclerosis, structural cardiac abnormality, cardiomyopathy, serious heart rhythm abnormalities, coronary artery disease, transient ischemic attack or stroke or other serious cardiac problems that may place them at increased vulnerability to the sympathomimetic effects of a stimulant drug. 9. History of controlled or uncontrolled hypertension or a resting supine systolic blood pressure \>139mmHg or diastolic blood pressure \>89mmHg. 10. Known family history of sudden cardiac death or ventricular arrhythmia. 11. Currently considered a suicide risk, has previously made a suicide attempt, or has a history of, or is currently demonstrating suicidal ideation. 12. Current use of any medication (including prescription, over-the-counter, herbal or homeopathic preparations) with the exception of hormonal replacement therapy or hormonal contraceptives (current use is defined as use within 14 days of first dose of investigational product). 13. Use of any medication known to inhibit or induce the cytochrome P450 (CYP450) enzymes responsible for the metabolism of the investigational product within 14 days of first dose of investigational product. 14. Known or suspected intolerance or hypersensitivity to the investigational product, closely related compounds, or any of the stated ingredients. 15. Known or suspected intolerance or hypersensitivity to orange juice or vanilla yogurt. 16. History of alcohol or other substance abuse within the last year. 17. A positive screen for alcohol or drugs of abuse at the Screening Visit or on Day 1 of Treatment Period 1. 18. Male subjects who consume more than 3 units of alcohol per day. Female subjects who consume more than 2 units of alcohol per day. (1 alcohol unit=1 beer=1 wine \[5oz\]=one liquor \[1.5 oz\]=0.75oz alcohol.). 19. A positive human immunodeficiency virus antibody screen, Hepatitis B surface antigen, or Hepatitis C virus antibody screen. 20. Use of tobacco in any form (eg, smoking or chewing) or other nicotine-containing products in any form (eg, gum, patch) within 30 days prior to the first dose of investigational product. 21. Routine consumption of more than 2 units of caffeine per day or subjects who experience caffeine withdrawal headaches or have a history of caffeine withdrawal headaches. (One caffeine unit is contained in the following items: one 6oz cup of coffee, two 12oz cans of cola, one 12oz cup of tea, three 1oz chocolate bars. Decaffeinated coffee, tea, or cola are not considered to contain caffeine). 22. Donation of blood or blood products (eg, plasma or platelets) within 60 days prior to the first dose of investigational product. 23. Use of another investigational product within 30 days prior to receiving the first dose of investigational product or active enrollment in another drug or vaccine clinical study. 24. Substantial changes in eating habits within 30 days prior to receiving the first dose of investigational product, as assessed by the investigator. 25. An inability to follow a standardized diet and meal schedule or inability to fast, as required during the study. 26. Prior screen failure, randomization, participation, or enrollment in this study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cmax for D-amphetamine | Up to 96 hours-post-dose | d-Amphetamine is a metabolite of Lisdexamfetamine Dimesylate and is an active form that is responsible for the drug's therapeutic activity. |
| Area Under the Plasma Concentration-time Curve (AUC) for Lisdexamfetamine Dimesylate | Up to 96 hours post-dose | AUC can be used as a measure of drug exposure. It is derived from drug concentration and time so it gives a measure how much and how long a drug stays in a body. |
| Maximum Plasma Concentration (Cmax) for Lisdexamfetamine Dimesylate | Up to 96 hours post-dose | Cmax is a term that refers to the maximum (or peak) concentration that a drug achieves in the body after the drug has been administrated. |
| AUC for D-amphetamine | Up to 96 hours post-dose | d-Amphetamine is a metabolite of Lisdexamfetamine Dimesylate and is an active form that is responsible for the drug's therapeutic activity. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Sequence 1 Lisdexamfetamine Dimesylate 70mg capsule mixed into orange juice for first intervention; then Lisdexamfetamine Dimesylate 70mg capsule mixed into vanilla yogurt for second intervention; then Lisdexamfetamine Dimesylate 70mg intact capsule fasting for third intervention | 5 |
| Sequence 2 Lisdexamfetamine Dimesylate 70mg capsule mixed into vanilla yogurt for first intervention; then Lisdexamfetamine Dimesylate 70mg intact capsule fasting for second intervention; then Lisdexamfetamine Dimesylate 70mg capsule mixed into orange juice for third intervention | 5 |
| Sequence 3 Lisdexamfetamine Dimesylate 70mg capsule mixed into vanilla yogurt for first intervention; then Lisdexamfetamine Dimesylate 70mg capsule mixed into orange juice for second intervention; then Lisdexamfetamine Dimesylate 70mg intact capsule fasting for third intervention | 5 |
| Sequence 4 Lisdexamfetamine Dimesylate 70mg capsule mixed into orange juice for first intervention; then Lisdexamfetamine Dimesylate 70mg intact capsule fasting for second intervention; then Lisdexamfetamine Dimesylate 70mg capsule mixed into vanilla yogurt for third intervention | 5 |
| Sequence 5 Lisdexamfetamine Dimesylate 70mg intact capsule fasting for first intervention; then Lisdexamfetamine Dimesylate 70mg capsule mixed into orange juice for second intervention; then Lisdexamfetamine Dimesylate 70mg capsule mixed into vanilla yogurt for third intervention | 5 |
| Sequence 6 Lisdexamfetamine Dimesylate 70mg intact capsule fasting for first intervention; then Lisdexamfetamine Dimesylate 70mg capsule mixed into vanilla yogurt for second intervention; then Lisdexamfetamine Dimesylate 70mg capsule mixed into orange juice for third intervention | 5 |
| Total | 30 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| Third Intervention | Withdrawal by Subject | 0 | 1 | 0 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | Sequence 1 | Sequence 2 | Sequence 3 | Sequence 4 | Sequence 5 | Sequence 6 | Total |
|---|---|---|---|---|---|---|---|
| Age, Continuous | 32.6 Years STANDARD_DEVIATION 10.16 | 35.4 Years STANDARD_DEVIATION 12.42 | 42.2 Years STANDARD_DEVIATION 4.44 | 34.2 Years STANDARD_DEVIATION 12.42 | 39.6 Years STANDARD_DEVIATION 9.86 | 41.8 Years STANDARD_DEVIATION 10.06 | 37.6 Years STANDARD_DEVIATION 10.07 |
| Age, Customized Between 18 and 65 years, inclusive | 5 Participants | 5 Participants | 5 Participants | 5 Participants | 5 Participants | 5 Participants | 30 Participants |
| Region of Enrollment UNITED STATES | 5 Participants | 5 Participants | 5 Participants | 5 Participants | 5 Participants | 5 Participants | 30 Participants |
| Sex: Female, Male Female | 1 Participants | 2 Participants | 1 Participants | 0 Participants | 2 Participants | 2 Participants | 8 Participants |
| Sex: Female, Male Male | 4 Participants | 3 Participants | 4 Participants | 5 Participants | 3 Participants | 3 Participants | 22 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 | 16 / 30 | 17 / 30 | 9 / 30 |
| serious Total, serious adverse events | 0 / 30 | 0 / 30 | 0 / 30 |
Outcome results
Primary
Area Under the Plasma Concentration-time Curve (AUC) for Lisdexamfetamine Dimesylate
AUC can be used as a measure of drug exposure. It is derived from drug concentration and time so it gives a measure how much and how long a drug stays in a body.
Time frame: Up to 96 hours post-dose
Population: Pharmacokinetic Set consisted of all subjects in the Safety Set for whom the primary pharmacokinetic data were considered sufficient and interpretable. Safety Set consisted of subjects who took at least 1 dose of investigational product and had at least 1 post-dose safety assessment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Lisdexamfetamine Dimesylate Mixed in Orange Juice | Area Under the Plasma Concentration-time Curve (AUC) for Lisdexamfetamine Dimesylate | 27.0 ng*hr/ml | Standard Deviation 7.8 |
| Lisdexamfetamine Dimesylate Mixed in Vanilla Yogurt | Area Under the Plasma Concentration-time Curve (AUC) for Lisdexamfetamine Dimesylate | 36.0 ng*hr/ml | Standard Deviation 14.2 |
| Lisdexamfetamine Dimesylate Intact Capsule Fasting | Area Under the Plasma Concentration-time Curve (AUC) for Lisdexamfetamine Dimesylate | 38.3 ng*hr/ml | Standard Deviation 12.3 |
90% CI: [0.655, 0.766]
90% CI: [0.849, 0.992]
Primary
AUC for D-amphetamine
d-Amphetamine is a metabolite of Lisdexamfetamine Dimesylate and is an active form that is responsible for the drug's therapeutic activity.
Time frame: Up to 96 hours post-dose
Population: Pharmacokinetic Set consisted of all subjects in the Safety Set for whom the primary pharmacokinetic data were considered sufficient and interpretable. Safety Set consisted of subjects who took at least 1 dose of investigational product and had at least 1 post-dose safety assessment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Lisdexamfetamine Dimesylate Mixed in Orange Juice | AUC for D-amphetamine | 1140.9 ng*h/ml | Standard Deviation 274.1 |
| Lisdexamfetamine Dimesylate Mixed in Vanilla Yogurt | AUC for D-amphetamine | 1110.1 ng*h/ml | Standard Deviation 252.9 |
| Lisdexamfetamine Dimesylate Intact Capsule Fasting | AUC for D-amphetamine | 1180.2 ng*h/ml | Standard Deviation 295.1 |
90% CI: [0.937, 1.004]
90% CI: [0.912, 0.977]
Primary
Cmax for D-amphetamine
d-Amphetamine is a metabolite of Lisdexamfetamine Dimesylate and is an active form that is responsible for the drug's therapeutic activity.
Time frame: Up to 96 hours-post-dose
Population: Pharmacokinetic Set consisted of all subjects in the Safety Set for whom the primary pharmacokinetic data were considered sufficient and interpretable. Safety Set consisted of subjects who took at least 1 dose of investigational product and had at least 1 post-dose safety assessment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Lisdexamfetamine Dimesylate Mixed in Orange Juice | Cmax for D-amphetamine | 59.1 ng/ml | Standard Deviation 9.47 |
| Lisdexamfetamine Dimesylate Mixed in Vanilla Yogurt | Cmax for D-amphetamine | 59.0 ng/ml | Standard Deviation 9.28 |
| Lisdexamfetamine Dimesylate Intact Capsule Fasting | Cmax for D-amphetamine | 61.0 ng/ml | Standard Deviation 10.81 |
90% CI: [0.945, 0.998]
90% CI: [0.944, 0.997]
Primary
Maximum Plasma Concentration (Cmax) for Lisdexamfetamine Dimesylate
Cmax is a term that refers to the maximum (or peak) concentration that a drug achieves in the body after the drug has been administrated.
Time frame: Up to 96 hours post-dose
Population: Pharmacokinetic Set consisted of all subjects in the Safety Set for whom the primary pharmacokinetic data were considered sufficient and interpretable. Safety Set consisted of subjects who took at least 1 dose of investigational product and had at least 1 post-dose safety assessment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Lisdexamfetamine Dimesylate Mixed in Orange Juice | Maximum Plasma Concentration (Cmax) for Lisdexamfetamine Dimesylate | 24.5 ng/ml | Standard Deviation 7.48 |
| Lisdexamfetamine Dimesylate Mixed in Vanilla Yogurt | Maximum Plasma Concentration (Cmax) for Lisdexamfetamine Dimesylate | 32.2 ng/ml | Standard Deviation 11.46 |
| Lisdexamfetamine Dimesylate Intact Capsule Fasting | Maximum Plasma Concentration (Cmax) for Lisdexamfetamine Dimesylate | 38.5 ng/ml | Standard Deviation 13.07 |
90% CI: [0.582, 0.707]
90% CI: [0.752, 0.912]