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`5. A Double-Blind, Ascending dose, Seven-Day Administration of Modafinil Tablets
`for Safety, Tolerance, And Pharmacokinetic Profile In Normal Male Subjects (CEP-
`2101).
`.
`-
`
`Objectives:
`To study the safety and PK ofmultiple dosing ofModafinil, and its enantiomers.
`
`Introduction:
` .
`
` .
`
`ran omized, placebo-controlled study evaluating PK of both modafinil and
`on e-
`its enantiomers in escalating doses for 7 days in healthy young male subjects.
`
`Study Design and Sampling:
`.
`A total of 32 volunteers, with 8 people in each of the following dose groups: 200
`mg/day, 400 mg/day, 600 mg/day, and 800 mg/day. In each dose group, 6 subjects were
`randomly assigned to receive the indicated dose ofmodafinil and 2 received placebo.
`Modafinil was administered orally in the form ofmultiple 100 mg tablets once daily with
`~3 00 ml of water one hour afier a light breakfast for 7 consecutive days. (Except subjects
`in the 800 mg/day dose group, who only received 3 daily doses, because ofsevere
`hypertension observed in one subject).
`administration ofthe next dosetLBjood samples ( [0 mL). drawn into lithium heparin
`vacutainers® (“green top“), were obtained immediately predosc (0 hr). and at 0.5. l, [5.
`2, 3. 4, 6. 8, and 12 hours after administration ofthe Day 1 dose. immediately predose (0
`
`hr trough sample) and 4 hours after dosing on Day 2 through Day 6, and immediately
`predose (0 hr). and at 0.5. l. 1.5, 2, 3. 4. 6, 8, 12, 24. and 48 hours after dosing on Dayfl
`The prepared plasma samples were shipped and stored at -20°C, or below. awaiting
`
`analysis.
`
`{Dune samples were collected at predose. 0.4, 4-8. 8- 12; 12-24 for Days [-7 and 24-48
`
`\hours post dose on Day 7. The urine volume was recorded. The urine samples were
`
`shipped and stored at -20°C. or below, awaiting analysis.
`
`.
`
`Results (Attachment 5) and Conclusions:
`The modafinil 800 mg dose group was terminated after 3 daily doses (due to an
`e event observed in subject #23), therefore, the PK parameters were not calculated
`
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`
`Comments:
`
`1. In this study, the apparent volume ofdistribution (V/F) ofthe cnantiomers of
`Modafinjl was calculated as V/F=Dose/(AUC(;inf *lamda), where Dose was that of
`Modafinil, mstead ofthe actual dose ofthe e
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`’ Protocol CEP-ZIOI: Phannacoldnetic Report
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