A Multicenter, Open-label, Flexible-Dose Extension Study Of Lurasidone Adjunctive To Lithium Or Divalproex In Subjects With Bipolar I Disorder
This is an open-label, multi-center, extension study designed to monitor the safety, tolerability and effectiveness of lurasidone for the treatment of subjects with bipolar I disorder who have participated in Study D1050296, [AND]amp;quot;A Randomized, Double-blind, Placebo-controlled, Flexible-dose, Parallel-group Study of Lurasidone Adjunctive to Lithium or Divalproex for the Prevention of Recurrence in Subjects with Bipolar I Disorder.[AND]amp;quot; Subjects will be evaluated for eligibility during the final study visit of Study D1050296. Subjects who have either completed double-blind treatment or experienced a protocol-specified recurrence of any mood event during the Double-blind Phase in study D1050296 will have the option to participate in this study. In addition, subjects who had at least entered the Open-label Phase of Study D1050296 when the Sponsor stopped the study will be eligible to enroll. Subjects who discontinued early from Study D1050296 for any other reason are not eligible to enroll in this study.
Informed consent will be obtained from all subjects before any study procedures are performed. Subjects who meet entry criteria will transition to this study directly from Study D1050296.
Subjects will be initially treated with open-label lurasidone 40 mg/day (Day 1). Dose adjustment of study drug (20, 40, 60 or 80 mg /day) should occur at the regularly scheduled visits and in increments/decrements of 1 dose level. If dose adjustment is required in between regular study visits, subject must come in for an unscheduled visit and return all used/unused medication kits at the time of dose adjustment. Dose reductions for tolerability or safety purposes are permitted to occur starting on the second day of extension study treatment (Day 2). These dose reductions may occur more frequently than the regular study visits and at more than 1 dose level at a time (maximum of 2 dose levels at a time) to optimize effectiveness and tolerability, based on Investigator judgment.
Subjects will be treated with open-label lithium or divalproex for the duration of the study and will be treated with the same drug (either lithium or divalproex) they received in the D1050296 study. During the study lithium and divalproex must be dosed to achieve serum trough concentrations of 0.4-1.2 mEq/L (0.4-1.2 mmol/L) and 50-125 [MICRO-SYMBOL]g/mL (346.5-866.3 umol/L), respectively.
All country-approved formulations of lithium or divalproex (including extended-release and controlled release formulations) dispensed by a pharmacy or comparable authorized retailer are permitted (with the exception of lithium orotate and magnesium valproate).
Safety and effectiveness assessments will be conducted throughout the study. A follow-up visit will occur 1 week post last dose of study drug.
1. Subject provides written informed consent and is willing and able to comply with the protocol, in the opinion of the Investigator.
2. Subject has completed the 28 week Double-blind Phase of Study D1050296 and all required assessments on the final study visit (Week 28, Visit 28); OR Subject has experienced a protocol-defined recurrence of any mood event during the Double-blind Phase of Study D1050296 and has completed all required assessments on the final study visit; OR Subject had at least entered the Open-label Phase of Study D1050296 when the Sponsor stopped the study and has completed all required assessments on the final study visit.
3. Subject is judged by the Investigator to be suitable for participation in a 12-week clinical study involving open-label lurasidone treatment.
4. Subject is not pregnant at the extension baseline visit (must have a negative urine pregnancy test at the final study visit in Study D1050296) or nursing (must not be lactating) and is not planning pregnancy within the projected duration of the study.
5. Males and female subjects who are of reproductive potential agree to remain abstinent or use adequate and reliable contraception throughout the study and for at least 30 days after the last dose of lurasidone has been taken. In the Investigator[Single Quote]s judgment, the subject will adhere to this requirement.
- Adequate contraception is defined as continuous use of either two barrier methods (eg, condom and spermicide or diaphragm with spermicide) or acceptable hormonal contraceptive. Acceptable hormonal contraceptives include thefollowing: a) contraceptive implant (such as Norplant(RegisteredTM)); b) injectable contraception (such as medroxyprogesterone acetate injection); or c) oral contraception.
-Female subjects who are of non-reproductive potential, ie, a subject who is surgically sterile, has undergone tubal ligation, or is postmenopausal (defined as at least 12 months of spontaneous amenorrhea or between 6 and 12 months of spontaneous amenorrhea with follicle stimulating hormone concentrations within postmenopausal range as determined by laboratory analysis) are not required to remain abstinent or use adequate contraception.
6. Subject is in good physical health on the basis of physical examination at the extension baseline visit (performed at the final study visit in Study D1050296).