Safety, Tolerability, and Pharmacokinetic Study of TV-447... | NCT06253546 | Trialant
NCT06253546
Sponsor
Teva Branded Pharmaceutical Products R&D LLC
Status
Completed
Last Update Posted
Jun 30, 2026Actual
Enrollment
24Actual
Phase
Phase 1
Conditions
Schizophrenia
Interventions
TV-44749 318mg
Oral Olanzapine 10mg/day
TV-44749 425mg
Oral Olanzapine 15mg/day
TV-44749 531mg
Oral Olanzapine 20mg/day
Countries
China
Protocol Section
Identification Module
NCT ID
NCT06253546
Obsolete or Duplicate NCT IDs
Not provided
Organization Study
TV44749-PK-10188
Secondary IDs
Not provided
Brief Title
Safety, Tolerability, and Pharmacokinetic Study of TV-44749 in Chinese Patients With Schizophrenia
Official Title
A Phase 1, Single Dose, Parallel Cohort Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of TV-44749, Olanzapine for Extended-Release Injectable Suspension for Subcutaneous Use, in Chinese Patients With Schizophrenia
Pediatric Postmarket Surveillance of a Device Product
Not provided
Product Exported from US
Not provided
FDAAA801 Violation
Not provided
Description Module
Brief Summary
Primary Objective:
To evaluate the safety and tolerability of single doses of TV-44749 for subcutaneous (sc) use in Chinese participants with schizophrenia.
Secondary Objectives:
To evaluate the pharmacokinetics (PK) of single doses of TV-44749 administered sc.
To evaluate the pharmacokinetics of oral olanzapine tablets following multiple dose administration.
To monitor the safety and tolerability of multiple doses of oral olanzapine tablets given in the study.
Detailed Description
The total study duration for participants is planned to be approximately 13 weeks, including 40 days of screening, 1-week oral olanzapine treatment, a 1-week washout period, 4-week TV-44749 treatment, and 2-week follow-up period after the last dosing interval.
Conditions Module
Conditions
Schizophrenia
Keywords
Not provided
Design Module
Study Type
Interventional
Number of References to an Expanded Access Study
Not provided
Expanded Access Types
Not provided
Patient Registry
Not provided
Target Follow-Up Duration
Not provided
Phases
Phase 1
Interventional Study Design
Allocation
Biospecimen
No data available
No data is available for this block.
Enrollment
24Actual
Arms/Interventions Module
Arm Groups
Label
Type
Description
Intervention Names
Cohort 1
Experimental
Period 1: Participants will receive oral olanzapine daily
Period 2: Participants will receive subcutaneous (sc) injection of TV-44749
Drug: TV-44749 318mg
Drug: Oral Olanzapine 10mg/day
Cohort 2
Experimental
Period 1: Participants will receive oral olanzapine daily
Period 2: Participants will receive sc injection of TV-44749
Drug: TV-44749 425mg
Drug: Oral Olanzapine 15mg/day
Cohort 3
Experimental
Period 1: Participants will receive oral olanzapine daily
Period 2: Participants will receive sc injection of TV-44749
Drug: TV-44749 531mg
Drug: Oral Olanzapine 20mg/day
Interventions
Name
Type
Description
Arm Group Labels
Other Names
TV-44749 318mg
Drug
Pharmaceutical form:
extended-release injectable suspension
Route of administration: subcutaneous injection
Cohort 1
Outcomes Module
Primary Outcomes
Measure
Description
Time Frame
Period 2: Number of Participants With Treatment Emergent Adverse Events (TEAEs)
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. Treatment-emergent AEs were defined as AEs that occurred after the first dose of study drug was administered in Period 1 through end of the trial. A summary of other non-serious AEs and all serious AEs (SAEs), regardless of causality is located in the Reported AE section.
Day 1 Up to Day 43
Period 2: Number of Participants With Treatment Emergent SAEs
An AE was defined as any untoward medical occurrence in a participant who received the study drug without regard to possibility of causal relationship. 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. Treatment-emergent AEs were defined as AEs that occurred after the first dose of study drug was administered in Period 1 through end of the trial. A summary of other non-serious AEs and all SAEs, regardless of causality is located in the Reported AE section.
Day 1 Up to Day 43
Period 2: Number of Participants With Injection Site AEs
Injection site AEs included injection site pruritus, induration, warmth, and abscess. A summary of other non-serious AEs and all SAEs, regardless of causality is located in the Reported AE section. All injection site AEs are reported in this outcome measure and the AE module only reports non-serious AEs at the 5% threshold. In the AE module, a participant could have been included for multiple injection site AEs.
Day 1 Up to Day 43
Secondary Outcomes
Measure
Description
Time Frame
Period 2: Maximum Observed Plasma Drug Concentration (Cmax) of TV-44749
Day 1 Up to Day 43
Period 2: Area Under the Plasma Drug Concentration-time Curve (AUC) Over the Period Following Administration on Day 1 to the Time of the Last Measurable Concentration (AUC0-t) of TV-44749
Other Outcomes
Not provided
Eligibility Module
Eligibility Criteria
Inclusion Criteria:
Body weight >50 kg and body mass index (BMI) between 18.5 to 38.0 kg/m2, inclusive, at the time of screening.
A current confirmed diagnosis of schizophrenia according to an evaluation by the investigator, using the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5)
Are clinically stable, on oral olanzapine (i.e., dose has not changed in the last 4 weeks), and not currently on other antipsychotic treatment at the time of screening.
No hospitalization for worsening of schizophrenic symptoms and no significant exacerbation of schizophrenic symptoms, as judged by the investigator, within the 3 months prior to screening.
Female participants must have a negative serum pregnancy test at screening, are sterile or postmenopausal, and not planning pregnancy within the study period and for an additional 6 months after last dose administration.
Male participants must be surgically sterile, or, if capable of producing offspring, has exclusively same-sex partners or is currently using an approved method of birth control.
Agree to maintain current smoking or nonsmoking status at the time informed consent is obtained and throughout the study until completion of the end of study (EOS)/early termination (ET) visit.
Have no ongoing or expected significant life events (such as pending loss of housing, marital status change, long travel abroad, surgery, etc.) that could affect study outcomes expected throughout the period of study participation.
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, musculoskeletal system or presence or history of clinically significant immunological, endocrine, metabolic, neurological, or psychiatric disorder(s) (other than schizophrenia), or a history of any illness that, in the opinion of the principal investigator, might pose additional risk to the participant by participation in the study or confound the results of the study
Major trauma or surgery in the 2 months before screening or at any time between screening and the first dose of the investigational medicinal product (IMP), surgery scheduled during the study or follow-up period, or open biopsy within 4 months prior to screening
History of malignancy or treatment of malignancy in the last 5 years, excluding resected basal cell or squamous cell carcinoma of the skin.
NOTE: Additional criteria apply, please contact the investigator for more information.
Accepts Healthy Volunteers
No
Sex
All
Sex/Gender Based
Not provided
Sex/Gender Description
Not provided
Minimum Age
18 Years
Maximum Age
64 Years
Standard Ages
Adult
Study Population
Not provided
Sampling Method
Not provided
Contacts/Locations Module
Central Contacts
Not provided
Overall Officials
Name
Affiliation
Role
Teva Medical Expert, MD
Teva Branded Pharmaceutical Products R&D LLC
Study Director
Locations
Facility
Status
City
State
ZIP
Country
Contacts
Teva Investigational Site 88049
Beijing
100088
China
Teva Investigational Site 88048
References Module
No data available
No data is available for this block.
IPD Sharing Statement Module
Plan to Share IPD
Yes
Description
Qualified researchers may request access to patient level data and related study documents including the study protocol and the statistical analysis plan. Requests will be assessed for scientific merit, product approval status, and conflicts of interest. If the request is approved, patient level data will be de-identified and study documents will be redacted to protect the privacy of trial participants and to protect commercially confidential information. Please email USMedInfo@tevapharm.com to make your request.
Types
Not provided
Time Frame
Not provided
Access Criteria
Not provided
URL
Not provided
Results Section
Participant Flow Module
Pre-assignment Details
A total of 36 participants were screened. Of these, 24 participants who met the eligibility criteria were enrolled and treated in Period 1 of the trial. A total of 21 participants who completed Period 1 were enrolled and treated in Period 2 of the trial.
Recruitment Details
Not provided
Type of Units Analyzed
Not provided
Arm/Group Information
ID
Title
Description
FG000
Period 1 Cohort 1: Olanzapine 10 mg/Day
Participants received oral olanzapine 10 milligrams (mg) once daily for 7 days (Day -14 to Day -8).
Period 2: AUC of TV-44749 Over the Period Following Administration on Day 1 Extrapolated to Infinity (AUC0-inf)
Day 1 Up to Day 43
Period 2: Time to Maximum Observed Concentration (Tmax) of TV-44749
Day 1 Up to Day 43
Period 2: Apparent Elimination Half-Life (t½) of TV-44749
Day 1 Up to Day 43
Period 1: Maximum Observed Plasma Drug Concentration at Steady State (Cmax,ss[Oral Olanzapine])
Day -8
Period 1: AUC of Oral Olanzapine From Time 0 to the End of the Dosing Interval (24 Hour) at Steady State (AUC0-tau,ss[Oral Olanzapine])
Day -8
Period 1: Calculated AUC of Oral Olanzapine at Steady State Extrapolated Over 28 Days (AUC0-tau,ss[Oral Olanzapine] * 28)
The steady-state AUC of oral olanzapine over a 28-day dosing interval was calculated by extrapolating the 24-hour AUC obtained following administration of the seventh oral dose (Day -8) to a 28-day period (AUC0-tau,ss[oral olanzapine] * 28).
Day -8 up to Day 20
Period 1: Time to Maximum Concentration of Oral Olanzapine at Steady State (Tmax,ss[Oral Olanzapine])
Day -8
Period 1: Number of Participants With TEAEs
An AE was defined as any untoward medical occurrence in a participant who received the study drug without regard to possibility of causal relationship. Treatment-emergent AEs were defined as AEs that occurred after the first dose of study drug was administered in Period 1 through end of the trial. A summary of other non-serious AEs and all SAEs, regardless of causality is located in the Reported AE section.
Day -14 up to Day -8
Period 1: Number of Participants With Treatment Emergent SAEs
An AE was defined as any untoward medical occurrence in a participant who received the study drug without regard to possibility of causal relationship. 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. Treatment-emergent AEs were defined as AEs that occurred after the first dose of study drug was administered in Period 1 through end of the trial. A summary of other non-SAEs and all serious AEs, regardless of causality is located in the Reported AE section.
Day -14 up to Day -8
Beijing
100191
China
Teva Investigational Site 88047
Guangzhou
510370
China
Teva Investigational Site 88046
Shanghai
200030
China
Teva Investigational Site 88050
Wuhan
430022
China
Teva Investigational Site 88056
Xi'an
710061
China
Participants received oral olanzapine 15 mg once daily for 7 days (Day -14 to Day -8).
FG002
Period 1 Cohort 3: Olanzapine 20 mg/Day
Participants received oral olanzapine 20 mg once daily for 7 days (Day -14 to Day -8).
FG003
Period 2 Cohort 1: TV44749 318 mg
Participants received single dose of TV-44749 318 mg administered subcutaneously (SC) on Day 1.
FG004
Period 2 Cohort 2: TV44749 425 mg
Participants received single dose of TV-44749 425 mg administered SC on Day 1.
FG005
Period 2 Cohort 3: TV44749 531 mg
Participants received single dose of TV-44749 531 mg administered SC on Day 1.
FG00012 subjects
FG0016 subjects
FG0026 subjects
FG0030 subjects
FG0040 subjects
FG0050 subjects
Received at Least 1 Dose of Study Drug
FG00012 subjects
FG0016 subjects
FG0026 subjects
FG0030 subjects
FG0040 subjects
FG0050 subjects
COMPLETED
FG00011 subjects
FG0014 subjects
FG0026 subjects
FG0030 subjects
FG0040 subjects
FG0050 subjects
NOT COMPLETED
FG0001 subjects
FG0012 subjects
FG0020 subjects
FG0030 subjects
FG0040 subjects
FG0050 subjects
Type
Comment
Reasons
Adverse Event
FG0000 subjects
FG0012 subjects
FG0020 subjects
FG0030 subjects
FG0040 subjects
FG0050 subjects
Other Than Specified
FG0001 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG004
TV-44749 Treatment & Follow-up (43 Days)
Type
Comment
Milestone Data
STARTED
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG00311 subjects
FG0044 subjects
FG0056 subjects
Received at Least 1 Dose of Study Drug
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG00311 subjects
COMPLETED
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG00311 subjects
FG004
NOT COMPLETED
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG004
The enrolled analysis set included all participants who signed an informed consent and were enrolled in the trial and received at least 1 oral olanzapine dose.
Type of Units Analyzed
Not provided
Arm/Group Information
ID
Title
Description
BG000
Period 1 Cohort 1: Olanzapine 10 mg/Day
Participants received oral olanzapine 10 mg once daily for 7 days (Day -14 to Day -8).
BG001
Period 1 Cohort 2: Olanzapine 15 mg/Day
Participants received oral olanzapine 15 mg once daily for 7 days (Day -14 to Day -8).
BG002
Period 1 Cohort 3: Olanzapine 20 mg/Day
Participants received oral olanzapine 20 mg once daily for 7 days (Day -14 to Day -8).
BG003
Total
Total of all reporting groups
Denominators
Units
Counts
Participants
BG00012
BG0016
BG0026
BG00324
Baseline Measures
Title
Description
Population Description
Parameter Type
Dispersion Type
Unit of Measure
Calculate Percentage
Denominator Units Selected
Denominators
Classes
Age, Continuous
Mean
Standard Deviation
years
Title
Denominators
Categories
Title
Measurements
BG00041.7± 12.82
BG00135.2± 11.30
BG00237.2± 12.61
BG003
Sex: Female, Male
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
Female
BG0003
BG0015
BG002
Ethnicity (NIH/OMB)
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
Hispanic or Latino
BG0000
BG0010
BG002
Race (NIH/OMB)
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
American Indian or Alaska Native
BG0000
BG0010
BG002
Type
Title
Description
Population Description
Reporting Status
Anticipated Posting Date
Parameter Type
Dispersion Type
Unit of Measure
Calculate Percentage
Time Frame
Units Analyzed
Denominator Units Selected
Arm/Group Information
Denominators
Classes
Analyses
Primary
Period 2: Number of Participants With Treatment Emergent Adverse Events (TEAEs)
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. Treatment-emergent AEs were defined as AEs that occurred after the first dose of study drug was administered in Period 1 through end of the trial. A summary of other non-serious AEs and all serious AEs (SAEs), regardless of causality is located in the Reported AE section.
The safety analysis set for Period 2 included all participants who received a SC injection of TV-44749.
Posted
Count of Participants
Participants
Day 1 Up to Day 43
ID
Title
Description
OG000
Period 2 Cohort 1: TV44749 318 mg
Participants received single dose of TV-44749 318 mg administered SC on Day 1.
OG001
Period 2 Cohort 2: TV44749 425 mg
Participants received single dose of TV-44749 425 mg administered SC on Day 1.
OG002
Period 2 Cohort 3: TV44749 531 mg
Participants received single dose of TV-44749 531 mg administered SC on Day 1.
Units
Counts
Participants
OG00011
OG0014
OG0026
Title
Denominators
Categories
Title
Measurements
OG00010
OG0013
OG0026
Primary
Period 2: Number of Participants With Treatment Emergent SAEs
An AE was defined as any untoward medical occurrence in a participant who received the study drug without regard to possibility of causal relationship. 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. Treatment-emergent AEs were defined as AEs that occurred after the first dose of study drug was administered in Period 1 through end of the trial. A summary of other non-serious AEs and all SAEs, regardless of causality is located in the Reported AE section.
The safety analysis set for Period 2 included all participants who received a SC injection of TV-44749.
Posted
Count of Participants
Participants
Day 1 Up to Day 43
ID
Title
Description
OG000
Period 2 Cohort 1: TV44749 318 mg
Participants received single dose of TV-44749 318 mg administered SC on Day 1.
OG001
Period 2 Cohort 2: TV44749 425 mg
Participants received single dose of TV-44749 425 mg administered SC on Day 1.
OG002
Period 2 Cohort 3: TV44749 531 mg
Primary
Period 2: Number of Participants With Injection Site AEs
Injection site AEs included injection site pruritus, induration, warmth, and abscess. A summary of other non-serious AEs and all SAEs, regardless of causality is located in the Reported AE section. All injection site AEs are reported in this outcome measure and the AE module only reports non-serious AEs at the 5% threshold. In the AE module, a participant could have been included for multiple injection site AEs.
The safety analysis set for Period 2 included all participants who received a SC injection of TV-44749.
Posted
Count of Participants
Participants
Day 1 Up to Day 43
ID
Title
Description
OG000
Period 2 Cohort 1: TV44749 318 mg
Participants received single dose of TV-44749 318 mg administered SC on Day 1.
OG001
Period 2 Cohort 2: TV44749 425 mg
Participants received single dose of TV-44749 425 mg administered SC on Day 1.
OG002
Period 2 Cohort 3: TV44749 531 mg
Participants received single dose of TV-44749 531 mg administered SC on Day 1.
Secondary
Period 2: Maximum Observed Plasma Drug Concentration (Cmax) of TV-44749
The pharmacokinetic (PK) analysis set for Period 2 included all participants who received a SC injection of TV-44749 and had sufficient data to calculate at least 1 PK parameter for TV-44749, where the participant had no events or deviations that would affect calculation of parameters.
Posted
Geometric Mean
Geometric Coefficient of Variation
nanograms (ng)/milliliter (mL)
Day 1 Up to Day 43
ID
Title
Description
OG000
Period 2 Cohort 1: TV44749 318 mg
Participants received single dose of TV-44749 318 mg administered SC on Day 1.
OG001
Period 2 Cohort 2: TV44749 425 mg
Participants received single dose of TV-44749 425 mg administered SC on Day 1.
OG002
Period 2 Cohort 3: TV44749 531 mg
Participants received single dose of TV-44749 531 mg administered SC on Day 1.
Units
Counts
Participants
Secondary
Period 2: Area Under the Plasma Drug Concentration-time Curve (AUC) Over the Period Following Administration on Day 1 to the Time of the Last Measurable Concentration (AUC0-t) of TV-44749
The PK analysis set for Period 2 included all participants who received a SC injection of TV-44749 and had sufficient data to calculate at least 1 PK parameter for TV-44749, where the participant had no events or deviations that would affect calculation of parameters.
Posted
Geometric Mean
Geometric Coefficient of Variation
hours*ng/mL
Day 1 Up to Day 43
ID
Title
Description
OG000
Period 2 Cohort 1: TV44749 318 mg
Participants received single dose of TV-44749 318 mg administered SC on Day 1.
OG001
Period 2 Cohort 2: TV44749 425 mg
Participants received single dose of TV-44749 425 mg administered SC on Day 1.
OG002
Period 2 Cohort 3: TV44749 531 mg
Participants received single dose of TV-44749 531 mg administered SC on Day 1.
Units
Counts
Secondary
Period 2: AUC of TV-44749 Over the Period Following Administration on Day 1 Extrapolated to Infinity (AUC0-inf)
The PK analysis set for Period 2 included all participants who received a SC injection of TV-44749 and had sufficient data to calculate at least 1 PK parameter for TV-44749, where the participant had no events or deviations that would affect calculation of parameters. 'Overall number of participants analyzed' = participants evaluable for this outcome measure.
Posted
Geometric Mean
Geometric Coefficient of Variation
hours*ng/mL
Day 1 Up to Day 43
ID
Title
Description
OG000
Period 2 Cohort 1: TV44749 318 mg
Participants received single dose of TV-44749 318 mg administered SC on Day 1.
OG001
Period 2 Cohort 2: TV44749 425 mg
Participants received single dose of TV-44749 425 mg administered SC on Day 1.
OG002
Period 2 Cohort 3: TV44749 531 mg
Participants received single dose of TV-44749 531 mg administered SC on Day 1.
Units
Counts
Secondary
Period 2: Time to Maximum Observed Concentration (Tmax) of TV-44749
The PK analysis set for Period 2 included all participants who received a SC injection of TV-44749 and had sufficient data to calculate at least 1 PK parameter for TV-44749, where the participant had no events or deviations that would affect calculation of parameters.
Posted
Median
Full Range
hours
Day 1 Up to Day 43
ID
Title
Description
OG000
Period 2 Cohort 1: TV44749 318 mg
Participants received single dose of TV-44749 318 mg administered SC on Day 1.
OG001
Period 2 Cohort 2: TV44749 425 mg
Participants received single dose of TV-44749 425 mg administered SC on Day 1.
OG002
Period 2 Cohort 3: TV44749 531 mg
Participants received single dose of TV-44749 531 mg administered SC on Day 1.
Units
Counts
Participants
Secondary
Period 2: Apparent Elimination Half-Life (t½) of TV-44749
The PK analysis set for Period 2 included all participants who received a SC injection of TV-44749 and had sufficient data to calculate at least 1 PK parameter for TV-44749, where the participant had no events or deviations that would affect calculation of parameters. 'Overall number of participants analyzed' = participants evaluable for this outcome measure.
Posted
Geometric Mean
Geometric Coefficient of Variation
hours
Day 1 Up to Day 43
ID
Title
Description
OG000
Period 2 Cohort 1: TV44749 318 mg
Participants received single dose of TV-44749 318 mg administered SC on Day 1.
OG001
Period 2 Cohort 2: TV44749 425 mg
Participants received single dose of TV-44749 425 mg administered SC on Day 1.
OG002
Period 2 Cohort 3: TV44749 531 mg
Participants received single dose of TV-44749 531 mg administered SC on Day 1.
Units
Counts
Participants
Secondary
Period 1: Maximum Observed Plasma Drug Concentration at Steady State (Cmax,ss[Oral Olanzapine])
The PK analysis set for Period 1 included all participants who received at least 1 dose of oral olanzapine and had sufficient data to calculate at least 1 PK parameter for oral olanzapine, where the participant had no events of emesis (following oral olanzapine), other events, or deviations that would affect calculation of parameters.
Posted
Geometric Mean
Geometric Coefficient of Variation
ng/mL
Day -8
ID
Title
Description
OG000
Period 1 Cohort 1: Olanzapine 10 mg/Day
Participants received oral olanzapine 10 mg once daily for 7 days (Day -14 to Day -8).
OG001
Period 1 Cohort 2: Olanzapine 15 mg/Day
Participants received oral olanzapine 15 mg once daily for 7 days (Day -14 to Day -8).
OG002
Period 1 Cohort 3: Olanzapine 20 mg/Day
Participants received oral olanzapine 20 mg once daily for 7 days (Day -14 to Day -8).
Units
Counts
Secondary
Period 1: AUC of Oral Olanzapine From Time 0 to the End of the Dosing Interval (24 Hour) at Steady State (AUC0-tau,ss[Oral Olanzapine])
The PK analysis set for Period 1 included all participants who received at least 1 dose of oral olanzapine and had sufficient data to calculate at least 1 PK parameter for oral olanzapine, where the participant had no events of emesis (following oral olanzapine), other events, or deviations that would affect calculation of parameters.
Posted
Geometric Mean
Geometric Coefficient of Variation
hours*ng/mL
Day -8
ID
Title
Description
OG000
Period 1 Cohort 1: Olanzapine 10 mg/Day
Participants received oral olanzapine 10 mg once daily for 7 days (Day -14 to Day -8).
OG001
Period 1 Cohort 2: Olanzapine 15 mg/Day
Participants received oral olanzapine 15 mg once daily for 7 days (Day -14 to Day -8).
OG002
Period 1 Cohort 3: Olanzapine 20 mg/Day
Participants received oral olanzapine 20 mg once daily for 7 days (Day -14 to Day -8).
Units
Secondary
Period 1: Calculated AUC of Oral Olanzapine at Steady State Extrapolated Over 28 Days (AUC0-tau,ss[Oral Olanzapine] * 28)
The steady-state AUC of oral olanzapine over a 28-day dosing interval was calculated by extrapolating the 24-hour AUC obtained following administration of the seventh oral dose (Day -8) to a 28-day period (AUC0-tau,ss[oral olanzapine] * 28).
The PK analysis set for Period 1 included all participants who received at least 1 dose of oral olanzapine and had sufficient data to calculate at least 1 PK parameter for oral olanzapine, where the participant had no events of emesis (following oral olanzapine), other events, or deviations that would affect calculation of parameters.
Posted
Geometric Mean
Geometric Coefficient of Variation
hours*ng/mL
Day -8 up to Day 20
ID
Title
Description
OG000
Period 1 Cohort 1: Olanzapine 10 mg/Day
Participants received oral olanzapine 10 mg once daily for 7 days (Day -14 to Day -8).
OG001
Period 1 Cohort 2: Olanzapine 15 mg/Day
Participants received oral olanzapine 15 mg once daily for 7 days (Day -14 to Day -8).
OG002
Period 1 Cohort 3: Olanzapine 20 mg/Day
Participants received oral olanzapine 20 mg once daily for 7 days (Day -14 to Day -8).
Secondary
Period 1: Time to Maximum Concentration of Oral Olanzapine at Steady State (Tmax,ss[Oral Olanzapine])
The PK analysis set for Period 1 included all participants who received at least 1 dose of oral olanzapine and had sufficient data to calculate at least 1 PK parameter for oral olanzapine, where the participant had no events of emesis (following oral olanzapine), other events, or deviations that would affect calculation of parameters.
Posted
Median
Full Range
hours
Day -8
ID
Title
Description
OG000
Period 1 Cohort 1: Olanzapine 10 mg/Day
Participants received oral olanzapine 10 mg once daily for 7 days (Day -14 to Day -8).
OG001
Period 1 Cohort 2: Olanzapine 15 mg/Day
Participants received oral olanzapine 15 mg once daily for 7 days (Day -14 to Day -8).
OG002
Period 1 Cohort 3: Olanzapine 20 mg/Day
Participants received oral olanzapine 20 mg once daily for 7 days (Day -14 to Day -8).
Units
Counts
Secondary
Period 1: Number of Participants With TEAEs
An AE was defined as any untoward medical occurrence in a participant who received the study drug without regard to possibility of causal relationship. Treatment-emergent AEs were defined as AEs that occurred after the first dose of study drug was administered in Period 1 through end of the trial. A summary of other non-serious AEs and all SAEs, regardless of causality is located in the Reported AE section.
The safety analysis set for Period 1 included all participants who received at least 1 dose of oral olanzapine.
Posted
Count of Participants
Participants
Day -14 up to Day -8
ID
Title
Description
OG000
Period 1 Cohort 1: Olanzapine 10 mg/Day
Participants received oral olanzapine 10 mg once daily for 7 days (Day -14 to Day -8).
OG001
Period 1 Cohort 2: Olanzapine 15 mg/Day
Participants received oral olanzapine 15 mg once daily for 7 days (Day -14 to Day -8).
OG002
Period 1 Cohort 3: Olanzapine 20 mg/Day
Participants received oral olanzapine 20 mg once daily for 7 days (Day -14 to Day -8).
Secondary
Period 1: Number of Participants With Treatment Emergent SAEs
An AE was defined as any untoward medical occurrence in a participant who received the study drug without regard to possibility of causal relationship. 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. Treatment-emergent AEs were defined as AEs that occurred after the first dose of study drug was administered in Period 1 through end of the trial. A summary of other non-SAEs and all serious AEs, regardless of causality is located in the Reported AE section.
The safety analysis set for Period 1 included all participants who received at least 1 dose of oral olanzapine.
Posted
Count of Participants
Participants
Day -14 up to Day -8
ID
Title
Description
OG000
Period 1 Cohort 1: Olanzapine 10 mg/Day
Participants received oral olanzapine 10 mg once daily for 7 days (Day -14 to Day -8).
OG001
Period 1 Cohort 2: Olanzapine 15 mg/Day
Participants received oral olanzapine 15 mg once daily for 7 days (Day -14 to Day -8).
OG002
Time Frame
Period 1: Day -14 up to Day -8; Period 2: Day 1 up to Day 43
Description
The safety analysis set for Period 1 included all participants who received at least 1 dose of oral olanzapine.
The safety analysis set for Period 2 included all participants who received a SC injection of TV-44749.
All-Cause Mortality Comment
Not provided
Arm/Groups
ID
Title
Description
Deaths (Affected)
Deaths (At Risk)
Serious Events (Affected)
Serious Events (At Risk)
Other Events (Affected)
Other Events (At Risk)
EG000
Period 1 Cohort 1: Olanzapine 10 mg/Day
Participants received oral olanzapine 10 mg once daily for 7 days (Day -14 to Day -8).
0
12
0
12
9
12
EG001
Period 1 Cohort 2: Olanzapine 15 mg/Day
Participants received oral olanzapine 15 mg once daily for 7 days (Day -14 to Day -8).
0
6
1
6
4
6
EG002
Period 1 Cohort 3: Olanzapine 20 mg/Day
Participants received oral olanzapine 20 mg once daily for 7 days (Day -14 to Day -8).
0
6
0
6
6
6
EG003
Period 2 Cohort 1: TV44749 318 mg
Participants received single dose of TV-44749 318 mg administered SC on Day 1.
0
11
0
11
10
11
EG004
Period 2 Cohort 2: TV44749 425 mg
Participants received single dose of TV-44749 425 mg administered SC on Day 1.
0
4
0
4
3
4
EG005
Period 2 Cohort 3: TV44749 531 mg
Participants received single dose of TV-44749 531 mg administered SC on Day 1.
0
6
1
6
6
6
Serious Adverse Events
Term
Organ System
Source Vocabulary
Assessment Type
Notes
Statistical Information
Sinus bradycardia
Cardiac disorders
MedDRA 26.0
Systematic Assessment
EG0000 events0 affected12 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG0030 events0 affected11 at risk
EG0040 events0 affected4 at risk
EG0051 events1 affected6 at risk
Schizophrenia
Psychiatric disorders
MedDRA 26.0
Systematic Assessment
EG0000 events0 affected12 at risk
EG0011 events1 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Other Adverse Events
Term
Organ System
Source Vocabulary
Assessment Type
Notes
Statistical Information
Atrioventricular conduction time shortened
Cardiac disorders
MedDRA 26.0
Systematic Assessment
EG0000 events0 affected12 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG0031 events1 affected11 at risk
EG0040 events0 affected4 at risk
EG0050 events0 affected6 at risk
Bundle branch block right
Cardiac disorders
MedDRA 26.0
Systematic Assessment
EG0000 events0 affected12 at risk
EG0010 events0 affected6 at risk
EG0021 events1 affected6 at risk
EG003
Mitral valve incompetence
Cardiac disorders
MedDRA 26.0
Systematic Assessment
EG0000 events0 affected12 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Sinus bradycardia
Cardiac disorders
MedDRA 26.0
Systematic Assessment
EG0001 events1 affected12 at risk
EG0012 events1 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Hyperprolactinaemia
Endocrine disorders
MedDRA 26.0
Systematic Assessment
EG0001 events1 affected12 at risk
EG0010 events0 affected6 at risk
EG0021 events1 affected6 at risk
EG003
Abdominal discomfort
Gastrointestinal disorders
MedDRA 26.0
Systematic Assessment
EG0000 events0 affected12 at risk
EG0010 events0 affected6 at risk
EG0021 events1 affected6 at risk
EG003
Diarrhoea
Gastrointestinal disorders
MedDRA 26.0
Systematic Assessment
EG0000 events0 affected12 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Fatigue
General disorders
MedDRA 26.0
Systematic Assessment
EG0000 events0 affected12 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Injection site induration
General disorders
MedDRA 26.0
Systematic Assessment
EG0000 events0 affected12 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Injection site pruritus
General disorders
MedDRA 26.0
Systematic Assessment
EG0000 events0 affected12 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Injection site warmth
General disorders
MedDRA 26.0
Systematic Assessment
EG0000 events0 affected12 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Injection site abscess
Infections and infestations
MedDRA 26.0
Systematic Assessment
EG0000 events0 affected12 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Upper respiratory tract infection
Infections and infestations
MedDRA 26.0
Systematic Assessment
EG0000 events0 affected12 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Urinary tract infection
Infections and infestations
MedDRA 26.0
Systematic Assessment
EG0000 events0 affected12 at risk
EG0011 events1 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Activated partial thromboplastin time prolonged
Investigations
MedDRA 26.0
Systematic Assessment
EG0000 events0 affected12 at risk
EG0011 events1 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Alanine aminotransferase increased
Investigations
MedDRA 26.0
Systematic Assessment
EG0001 events1 affected12 at risk
EG0010 events0 affected6 at risk
EG0022 events2 affected6 at risk
EG003
Aspartate aminotransferase increased
Investigations
MedDRA 26.0
Systematic Assessment
EG0000 events0 affected12 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Blood cholesterol increased
Investigations
MedDRA 26.0
Systematic Assessment
EG0000 events0 affected12 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Blood creatine phosphokinase increased
Investigations
MedDRA 26.0
Systematic Assessment
EG0000 events0 affected12 at risk
EG0012 events1 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Blood glucose increased
Investigations
MedDRA 26.0
Systematic Assessment
EG0000 events0 affected12 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Blood pressure increased
Investigations
MedDRA 26.0
Systematic Assessment
EG0000 events0 affected12 at risk
EG0011 events1 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Blood prolactin abnormal
Investigations
MedDRA 26.0
Systematic Assessment
EG0000 events0 affected12 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Blood prolactin increased
Investigations
MedDRA 26.0
Systematic Assessment
EG0000 events0 affected12 at risk
EG0011 events1 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Electrocardiogram QT prolonged
Investigations
MedDRA 26.0
Systematic Assessment
EG0000 events0 affected12 at risk
EG0011 events1 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Electrocardiogram repolarisation abnormality
Investigations
MedDRA 26.0
Systematic Assessment
EG0000 events0 affected12 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Gamma-glutamyltransferase increased
Investigations
MedDRA 26.0
Systematic Assessment
EG0000 events0 affected12 at risk
EG0010 events0 affected6 at risk
EG0021 events1 affected6 at risk
EG003
Heart rate increased
Investigations
MedDRA 26.0
Systematic Assessment
EG0000 events0 affected12 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Platelet count decreased
Investigations
MedDRA 26.0
Systematic Assessment
EG0001 events1 affected12 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Prothrombin time prolonged
Investigations
MedDRA 26.0
Systematic Assessment
EG0000 events0 affected12 at risk
EG0011 events1 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Weight decreased
Investigations
MedDRA 26.0
Systematic Assessment
EG0001 events1 affected12 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Weight increased
Investigations
MedDRA 26.0
Systematic Assessment
EG0000 events0 affected12 at risk
EG0012 events2 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Hypercholesterolaemia
Metabolism and nutrition disorders
MedDRA 26.0
Systematic Assessment
EG0001 events1 affected12 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Hyperglycaemia
Metabolism and nutrition disorders
MedDRA 26.0
Systematic Assessment
EG0001 events1 affected12 at risk
EG0010 events0 affected6 at risk
EG0021 events1 affected6 at risk
EG003
Hyperlipidaemia
Metabolism and nutrition disorders
MedDRA 26.0
Systematic Assessment
EG0000 events0 affected12 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Hyperphosphataemia
Metabolism and nutrition disorders
MedDRA 26.0
Systematic Assessment
EG0000 events0 affected12 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Hypertriglyceridaemia
Metabolism and nutrition disorders
MedDRA 26.0
Systematic Assessment
EG0000 events0 affected12 at risk
EG0014 events2 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Hyperuricaemia
Metabolism and nutrition disorders
MedDRA 26.0
Systematic Assessment
EG0000 events0 affected12 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Arthralgia
Musculoskeletal and connective tissue disorders
MedDRA 26.0
Systematic Assessment
EG0001 events1 affected12 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Akathisia
Nervous system disorders
MedDRA 26.0
Systematic Assessment
EG0000 events0 affected12 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Dizziness
Nervous system disorders
MedDRA 26.0
Systematic Assessment
EG0001 events1 affected12 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Somnolence
Nervous system disorders
MedDRA 26.0
Systematic Assessment
EG0000 events0 affected12 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Insomnia
Psychiatric disorders
MedDRA 26.0
Systematic Assessment
EG0003 events3 affected12 at risk
EG0010 events0 affected6 at risk
EG0022 events2 affected6 at risk
EG003
Schizophrenia
Psychiatric disorders
MedDRA 26.0
Systematic Assessment
EG0001 events1 affected12 at risk
EG0011 events1 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Pollakiuria
Renal and urinary disorders
MedDRA 26.0
Systematic Assessment
EG0000 events0 affected12 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Cough
Respiratory, thoracic and mediastinal disorders
MedDRA 26.0
Systematic Assessment
EG0000 events0 affected12 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Cystic lung disease
Respiratory, thoracic and mediastinal disorders
MedDRA 26.0
Systematic Assessment
EG0001 events1 affected12 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Oropharyngeal pain
Respiratory, thoracic and mediastinal disorders
MedDRA 26.0
Systematic Assessment
EG0000 events0 affected12 at risk
EG0010 events0 affected6 at risk
EG0021 events1 affected6 at risk
EG003
Hypotension
Vascular disorders
MedDRA 26.0
Systematic Assessment
EG0000 events0 affected12 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Certain Agreements
Are all PI(s) employees of the sponsor?
No
Restriction Type
OTHER
Results Disclosure Restriction on PI(s)?
Yes
Other Details
Sponsor has the right 60 days before submission for publication to review/provide comments. If the Sponsor's review shows that potentially patentable subject matter would be disclosed, publication or public disclosure shall be delayed for up to 90 additional days in order for the Sponsor, or Sponsor's designees, to file the necessary patent applications. In multicenter trials, each PI will postpone single center publications until after disclosure or publication of multicenter data.