Schizophrenia, Schizoaffective Disorder
Conditions
Brief summary
The primary objective of the study is to characterize the pharmacokinetics of 3 formulations of olanzapine. A secondary objective is to evaluate the safety and tolerability of 3 formulations of olanzapine. Another secondary objective is to characterize the pharmacokinetics of ZYPREXA. The planned duration of the study for each participant is 19 weeks.
Detailed description
All participants received immediate-release ZYPREXA and then were randomized into 1 of 3 extended-release olanzapine formulations.
Interventions
DRUGOlanzapine Extended Release
Powder and vehicle for injectable suspension
DRUGOlanzapine Immediate Release
IntraMuscular Injection
Sponsors
Teva Branded Pharmaceutical Products R&D LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 64 Years
Healthy volunteers
No
Inclusion criteria
* Body weight \>50 kg and body mass index (BMI) within the range 18.5 to 38.0 kg/m2, inclusive, at the time of screening * Agree to maintain current smoking or nonsmoking status at the time informed consent is obtained and throughout the trial until completion of the end of treatment or early termination (ET) visit (ie, nonsmoking participants must agree not to start smoking and participants who smoke will be excluded if they plan to discontinue smoking during the trial * Agree to the inpatient periods required during the trial period * Have a current confirmed diagnosis of schizophrenia or schizoaffective disorder according to an evaluation by the Investigator, using the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) (American Psychiatric Association 2013a) * Have no ongoing or expected significant life events (eg, pending loss of housing, marital status change, long travel abroad, surgery) that could affect trial outcomes throughout the period of trial participation * Women may be included only if they have a negative serum beta human chorionic gonadotropin (HCG) test result at screening; they are surgically sterile (hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or postmenopausal * Men must be sterile; or if they are potentially of reproductive competence and have sexual relationship with female partners of childbearing potential, they must use, together with their female partners, highly effective birth control methods for the duration of the trial and for 70 days after the last dose administration NOTE- Additional criteria apply, please contact the investigator for more information
Exclusion criteria
* Presence or have a history of clinically significant diseases of the renal, hepatic, gastrointestinal, cardiovascular, or musculoskeletal system, or presence or history of clinically significant immunological, endocrine, or metabolic diseases, neurological or psychiatric disorder(s) (other than schizophrenia) * History or known risk of narrow-angle glaucoma * Uncontrolled diabetes * Major trauma or surgery in the 2 months before screening * History of malignancy or treatment of malignancy in the last 5 years, excluding resected basal cell or squamous cell carcinoma of the skin * The participant is a pregnant or lactating woman or plans to become pregnant during the trial or within 70 days after the last dose administration * Personal or family history of arrhythmia, sudden unexplained death at a young age (before 40 years) in a first-degree relative, long QT syndrome, personal history of syncope, or history of uncontrolled high blood pressure NOTE- Additional criteria apply, please contact the investigator for more information
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Area Under the Plasma Concentration-time Curve From Study Drug Administration to the Last Measurable Concentration (AUC0-t) of Olanzapine (Extended-release Formulation) | Randomization Day 1 to 84 days after randomization |
| Area Under the Plasma Concentration-time Curve Extrapolated to Infinity (AUC0-inf) of Olanzapine (Extended-release Formulation) | Randomization Day 1 to 84 days after randomization |
| Maximum Observed Plasma Concentration (Cmax) of Olanzapine (Extended-release Formulation) | Randomization Day 1 to 84 days after randomization |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| AUC0-t of ZYPREXA (Immediate-release Formulation) | Predose (Day 4) up to 216 hours after administration of ZYPREXA (Day 13) | — |
| Number of Participants With at Least 1 Serious Adverse Event (SAE) Over the 28-day Period Following Administration of 1 of the SC Olanzapine Formulations | Randomization Day 1 through Randomization Day 29 | The SAEs were defined as death, a life-threatening AE, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity, a congenital anomaly or birth defect, or an important medical event that jeopardized participant and required medical intervention to prevent 1 of the outcomes listed in this definition. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in the Reported AE section. |
| Apparent Plasma Terminal Elimination Rate Constant (λz) of ZYPREXA (Immediate-release Formulation) | Predose (Day 4) up to 216 hours after administration of ZYPREXA (Day 13) | — |
| Number of Participants With at Least 1 Treatment-emergent Adverse Event (TEAE) Over the 28-day Period Following Administration of 1 of the SC Olanzapine Formulations | Randomization Day 1 through Randomization Day 29 | An adverse event (AE) was defined as any untoward medical occurrence in a participant who received the study drug without regard to possibility of causal relationship. A TEAE was defined as an AE that occurred after the first dose of study drug administration through the end of trial. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in the Reported AE section. |
| Cmax of ZYPREXA (Immediate-release Formulation) | Up to 24 hours after administration of ZYPREXA (Day 4) | — |
Countries
United States
Contacts
STUDY_DIRECTORTeva Medical Expert, MD
Teva Branded Pharmaceutical Products R&D, Inc.
Participant flow
Pre-assignment details
A total of 183 participants signed the informed consent form for screening. Of these, 106 participants met eligibility criteria and were enrolled in the study. 91 participants were randomized to treatment arms.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 42.8 years STANDARD_DEVIATION 11.72 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 7 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 22 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race/Ethnicity, Customized Race Asian | 2 Participants |
| Race/Ethnicity, Customized Race Black or African American | 64 Participants |
| Race/Ethnicity, Customized Race Native Hawaiian or Other Pacific Islander | 1 Participants |
| Race/Ethnicity, Customized Race Other | 2 Participants |
| Race/Ethnicity, Customized Race White | 6 Participants |
| Sex: Female, Male Female | 11 Participants |
| Sex: Female, Male Male | 13 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 106 | 0 / 29 | 0 / 31 | 0 / 31 |
| other Total, other adverse events | 18 / 98 | 8 / 29 | 11 / 31 | 6 / 31 |
| serious Total, serious adverse events | 0 / 98 | 0 / 29 | 1 / 31 | 0 / 31 |
Outcome results
None listed