Schizophrenia Schizoaffective
Conditions
Brief summary
Lyndra is developing an oral, extended release (ER) formulation of risperidone (LYN-005) presented in a capsule dosage form with the intent of reducing the frequency of dosing orally-administered medications to once weekly or less and thereby improving the management of schizophrenia. Study LYN-005-C-004 will evaluate the safety, tolerability, and pharmacokinetics (PK) of multiple dose administration of the ER formulation at two dose levels of LYN-005 relative to IR risperidone.
Detailed description
LYN-005-C-004 is a blinded, multiple-dose, randomized, parallel group, safety, tolerability and PK study of LYN-005 in subjects with a primary diagnosis of schizophrenia or schizoaffective disorder in general good health. Eligible subjects must be clinically stable and receiving a therapeutic dose of an approved oral antipsychotic drug for a minimum of 6 weeks at the time of Screening. Enrolled subjects will be evaluated under steady-state conditions on commercially-available IR risperidone tablets and then assigned in blinded fashion either to LYN-005 weekly or continued encapsulated IR risperidone daily for 3 weeks to attain (or continue) steady-state exposure.
Interventions
DRUGLYN-005
LYN-005 (14 or 28 mg weekly) plus IR risperidone matched placebo.
Sponsors
Worldwide Clinical Trials
Lyndra Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Caregiver)
Masking description
Although treatment assignment was blinded; the dose level was not blinded. The dose of LYN-005 (14 or 28 mg)/IR risperidone (2 or 4 mg/day) administered was based on the subject's current antipsychotic medication dose. Randomization was stratified by risperidone dose (LYN-005 14 mg/IR risperidone 2 mg/day \[low dose\] and LYN-005 28 mg/IR risperidone 4 mg/day \[high dose\], with a maximum of 16 subjects enrolled in each stratum. Within each stratum, subjects were randomized on a 3:1 basis to either LYN-005 or risperidone, respectively.
Intervention model description
LYN-005-C-004 was a blinded, multiple-dose, randomized, parallel group, safety, tolerability and PK study of LYN-005 in subjects with a primary diagnosis of schizophrenia or schizoaffective disorder in general good health. Eligible subjects were clinically stable and receiving a therapeutic dose of an approved oral antipsychotic drug for a minimum of 6 weeks at the time of Screening. Enrolled subjects were evaluated under steady-state conditions on commercially-available IR risperidone tablets and then assigned in blinded fashion either to LYN-005 weekly or continued encapsulated IR risperidone daily for 3 weeks to attain (or continue) steady-state exposure.
Eligibility
Sex/Gender
ALL
Age
18 Years to 50 Years
Healthy volunteers
No
Inclusion criteria
Eligibility for this study was met if each one of the following inclusion criteria was satisfied at Screening (or at baseline when specified): 1. Male or female aged ≥18 and ≤50 years. 2. Current diagnosis of schizophrenia or schizoaffective disorder according to DSM-5 criteria as confirmed by the MINI 7.0.2. 3. The following psychiatric criteria were used to determine subject eligibility: 1. Duration of diagnosis of schizophrenia or schizoaffective disorder of ≥2 years. 2. Outpatient; not hospitalized for worsening of schizophrenia within the last 6 months (partial hospitalization for social management within this time period is acceptable). 3. Medically stable over the last month and psychiatrically stable without significant symptom exacerbation over the last 3 months. 4. Stabilized on an oral antipsychotic medication (single agent) for a minimum of 6 weeks at the time of Screening. 5. On a stable dosage of all permitted non-antipsychotic medications (except for medication to be used on an as-needed basis) for at least 1 month prior to the Screening visit and for the duration of the study. 6. CGI-S score of ≤4 (moderately ill). 7. PANSS score of ≤80 points. 8. Body mass index (BMI) of ≥18 kg/m2 and ≤35 kg/m2. 9. Able to read and understand study procedures and provide written informed consent before the initiation of any protocol-specific procedures. 10. Willing to comply with all protocol-specified procedures and availability for the duration of the study. 11. Subject has identified a caregiver or personal contact with whom the subject communicates with at least once a week.
Exclusion criteria
Subject will not be considered eligible to participate in this study if any one of the following
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Active Moiety Tmax | Reported data was obtained following multiple dose administration of 3 weekly doses [(IR, Day-1), (ER, Week 1), ER Week 3)] of 14 or 28 mg risperidone LYN-005 capsules to assess extended release PK. | Active Moiety Tmax (h) (risperidone and 9-hydroxyrisperidone combined) after repeat weekly doses of LYN-005 ER capsules relative to IR risperidone tablets at 2 dose levels. |
| Participants With at Least One Treatment Emergent Adverse Event (TEAE). | 35 days | Incidence of treatment emergent adverse events (TEAEs) reported as participants with at least one treatment emergent adverse event (TEAE). |
| Total Number of Treatment Emergent Adverse Events (TEAEs). | 35 days | Incidence of treatment emergent adverse events (TEAEs) reported as total number of TEAEs. |
| Active Moiety PK (Cmax) | Reported data was obtained following multiple dose administration of 3 weekly doses [(IR, Day-1), (ER, Week 1), ER Week 3)] of 14 or 28 mg risperidone LYN-005 capsules to assess extended release PK. | Active moiety Cmax (risperidone and 9-hydroxyrisperidone combined) after repeat weekly doses of LYN-005 Extended Release (ER) capsules relative to Immediate Release (IR) risperidone tablets at 2 dose levels. |
| Active Moiety PK (AUC0-24, AUC0-168) | Reported data was obtained following multiple dose administration of 3 weekly doses [(IR, Day-1), (ER, Week 1), ER Week 3)] of 14 or 28 mg risperidone LYN-005 capsules to assess extended release PK. | Active moiety AUC (risperidone and 9-hydroxyrisperidone combined) after repeat weekly doses of LYN-005 ER capsules relative to IR risperidone tablets at 2 dose levels. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| PK of Risperidone (Cmax). | Reported data was obtained following multiple dose administration of 3 weekly doses [(IR, Day-1), (ER, Week 1), ER Week 3)] of 14 or 28 mg risperidone LYN-005 capsules to assess extended release PK. | To characterize exposure (Cmax) of risperidone during the switch to LYN-005. |
| PK of Risperidone (AUC0-24h, AUC0-168). | Reported data was obtained following multiple dose administration of 3 weekly doses [(IR, Day-1), (ER, Week 1), ER Week 3)] of 14 or 28 mg risperidone LYN-005 capsules to assess extended release PK. | To characterize exposure (AUC0-24h, AUC0-168) of risperidone during the switch to LYN-005. |
| PK of 9-Hydroxyrisperidone (Cmax). | Reported data was obtained following multiple dose administration of 3 weekly doses [(IR, Day-1), (ER, Week 1), ER Week 3)] of 14 or 28 mg risperidone LYN-005 capsules to assess extended release PK. | To characterize exposure (Cmax) of 9-Hydroxyrisperidone during the switch to LYN-005. |
| PK of 9-Hydroxyrisperidone (AUC0-24h, AUC0-168h). | Reported data was obtained following multiple dose administration of 3 weekly doses [(IR, Day-1), (ER, Week 1), ER Week 3)] of 14 or 28 mg risperidone LYN-005 capsules to assess extended release PK. | To characterize exposure (AUC0-24h, AUC0-168h) of 9-Hydroxyrisperidone during the switch to LYN-005. |
Countries
United States
Participant flow
Recruitment details
This study was conducted at 5 sites that randomized participants in the US. The study period was 13 August 2020 (first signed informed consent) to 22 December 2020 (last participant visit/observation)
Pre-assignment details
A total of 34 participants were enrolled. Thirty-two participants completed the Run-in Period and were randomized, comprising the Safety Population; of these, 24 participants received LYN-005 (12 low dose; 12 high dose) and 8 participants received IR risperidone (4 low dose; 4 high dose).
Participants by arm
| Arm | Count |
|---|---|
| LYN-005 14 mg LYN-005: Size 00EL capsules containing LYN-005 stellate (14mg)
AND
IR risperidone matched placebo | 12 |
| LYN-005 28 mg LYN-005: Size 00EL capsules containing LYN-005 stellate (28 mg)
AND
IR risperidone matched placebo | 12 |
| Risperidone 2 mg Risperidone (2 mg)
AND
LYN-005-matched placebo | 4 |
| Risperidone 4 mg Risperidone (4 mg)
AND
LYN-005-matched placebo. | 4 |
| Total | 32 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 1 | 1 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 2 | 0 | 0 | 1 |
Baseline characteristics
| Characteristic | Total | LYN-005 14 mg | LYN-005 28 mg | Risperidone 2 mg | Risperidone 4 mg |
|---|---|---|---|---|---|
| Age, Continuous | 36.2 years STANDARD_DEVIATION 7.28 | 36.0 years STANDARD_DEVIATION 6.24 | 34.3 years STANDARD_DEVIATION 7.46 | 35.0 years STANDARD_DEVIATION 7.12 | 43.5 years STANDARD_DEVIATION 7.85 |
| Body Mass Index (BMI) | 27.11 kg/m^2 STANDARD_DEVIATION 4.835 | 29.57 kg/m^2 STANDARD_DEVIATION 4.695 | 24.98 kg/m^2 STANDARD_DEVIATION 4.476 | 26.48 kg/m^2 STANDARD_DEVIATION 2.68 | 26.78 kg/m^2 STANDARD_DEVIATION 6.086 |
| CGI-S Total Score at Baseline | 3.0 units on a scale STANDARD_DEVIATION 0.65 | 2.9 units on a scale STANDARD_DEVIATION 0.51 | 3.0 units on a scale STANDARD_DEVIATION 0.85 | 2.8 units on a scale STANDARD_DEVIATION 0.5 | 3.3 units on a scale STANDARD_DEVIATION 0.5 |
| ESRS Total Score at Baseline | 0.4 units on a scale STANDARD_DEVIATION 1.36 | 0.2 units on a scale STANDARD_DEVIATION 0.58 | 0.6 units on a scale STANDARD_DEVIATION 2.02 | 0 units on a scale STANDARD_DEVIATION 0 | 0.8 units on a scale STANDARD_DEVIATION 1.5 |
| Race/Ethnicity, Customized Race Black or African American | 30 Participants | 11 Participants | 11 Participants | 4 Participants | 4 Participants |
| Race/Ethnicity, Customized Race White | 2 Participants | 1 Participants | 1 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Female | 6 Participants | 2 Participants | 3 Participants | 1 Participants | 0 Participants |
| Sex: Female, Male Male | 26 Participants | 10 Participants | 9 Participants | 3 Participants | 4 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 / 12 | 0 / 12 | 0 / 4 | 0 / 4 |
| other Total, other adverse events | 10 / 12 | 8 / 12 | 1 / 4 | 1 / 4 |
| serious Total, serious adverse events | 0 / 12 | 0 / 12 | 0 / 4 | 0 / 4 |
Outcome results
Primary
Active Moiety PK (AUC0-24, AUC0-168)
Active moiety AUC (risperidone and 9-hydroxyrisperidone combined) after repeat weekly doses of LYN-005 ER capsules relative to IR risperidone tablets at 2 dose levels.
Time frame: Reported data was obtained following multiple dose administration of 3 weekly doses [(IR, Day-1), (ER, Week 1), ER Week 3)] of 14 or 28 mg risperidone LYN-005 capsules to assess extended release PK.
Population: All enrolled participants who received at least 1 dose of randomized study drug and had at least 1 post-dose quantifiable (or evaluable) PK concentration data
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| LYN-005 14mg | Active Moiety PK (AUC0-24, AUC0-168) | AUC0-24 | 377 h*ng/mL | Geometric Coefficient of Variation 44 |
| LYN-005 28mg | Active Moiety PK (AUC0-24, AUC0-168) | AUC0-24 | 361 h*ng/mL | Geometric Coefficient of Variation 49 |
| LYN-005 28mg | Active Moiety PK (AUC0-24, AUC0-168) | AUC0-168 | 1820 h*ng/mL | Geometric Coefficient of Variation 52.1 |
| Overall LYN-005 | Active Moiety PK (AUC0-24, AUC0-168) | AUC0-24 | 371 h*ng/mL | Geometric Coefficient of Variation 47.4 |
| Overall LYN-005 | Active Moiety PK (AUC0-24, AUC0-168) | AUC0-168 | 2120 h*ng/mL | Geometric Coefficient of Variation 53.2 |
| Risperidone 2 mg | Active Moiety PK (AUC0-24, AUC0-168) | AUC0-24 | 301 h*ng/mL | Geometric Coefficient of Variation 23.1 |
| Risperidone 4 mg | Active Moiety PK (AUC0-24, AUC0-168) | AUC0-24 | 326 h*ng/mL | Geometric Coefficient of Variation 19.1 |
| Overall Risperidone | Active Moiety PK (AUC0-24, AUC0-168) | AUC0-24 | 359 h*ng/mL | Geometric Coefficient of Variation 32.6 |
| LYN-005 28 mg (A) | Active Moiety PK (AUC0-24, AUC0-168) | AUC0-24 | 472 h*ng/mL | Geometric Coefficient of Variation 137.7 |
| LYN-005 28 mg (B) | Active Moiety PK (AUC0-24, AUC0-168) | AUC0-24 | 575 h*ng/mL | Geometric Coefficient of Variation 39.3 |
| LYN-005 28 mg (B) | Active Moiety PK (AUC0-24, AUC0-168) | AUC0-168 | 3350 h*ng/mL | Geometric Coefficient of Variation 42.3 |
| LYN-005 28 mg (C) | Active Moiety PK (AUC0-24, AUC0-168) | AUC0-168 | 2950 h*ng/mL | Geometric Coefficient of Variation 121.1 |
| LYN-005 28 mg (C) | Active Moiety PK (AUC0-24, AUC0-168) | AUC0-24 | 568 h*ng/mL | Geometric Coefficient of Variation 104.3 |
| Risperidone 4 mg (A) | Active Moiety PK (AUC0-24, AUC0-168) | AUC0-24 | 732 h*ng/mL | Geometric Coefficient of Variation 46.3 |
| Risperidone 4 mg (B) | Active Moiety PK (AUC0-24, AUC0-168) | AUC0-24 | 753 h*ng/mL | Geometric Coefficient of Variation 44.9 |
| Risperidone 4 mg (C) | Active Moiety PK (AUC0-24, AUC0-168) | AUC0-24 | 687 h*ng/mL | Geometric Coefficient of Variation 36.9 |
Primary
Active Moiety PK (Cmax)
Active moiety Cmax (risperidone and 9-hydroxyrisperidone combined) after repeat weekly doses of LYN-005 Extended Release (ER) capsules relative to Immediate Release (IR) risperidone tablets at 2 dose levels.
Time frame: Reported data was obtained following multiple dose administration of 3 weekly doses [(IR, Day-1), (ER, Week 1), ER Week 3)] of 14 or 28 mg risperidone LYN-005 capsules to assess extended release PK.
Population: All enrolled participants who received at least 1 dose of randomized study drug and had at least 1 post-dose quantifiable (or evaluable) PK concentration data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| LYN-005 14mg | Active Moiety PK (Cmax) | 31.0 ng/mL | Geometric Coefficient of Variation 37.5 |
| LYN-005 28mg | Active Moiety PK (Cmax) | 20.0 ng/mL | Geometric Coefficient of Variation 56.7 |
| Overall LYN-005 | Active Moiety PK (Cmax) | 18.6 ng/mL | Geometric Coefficient of Variation 42.9 |
| Risperidone 2 mg | Active Moiety PK (Cmax) | 24.8 ng/mL | Geometric Coefficient of Variation 38.3 |
| Risperidone 4 mg | Active Moiety PK (Cmax) | 30.3 ng/mL | Geometric Coefficient of Variation 17.5 |
| Overall Risperidone | Active Moiety PK (Cmax) | 31.2 ng/mL | Geometric Coefficient of Variation 68.7 |
| LYN-005 28 mg (A) | Active Moiety PK (Cmax) | 24.6 ng/mL | Geometric Coefficient of Variation 405.7 |
| LYN-005 28 mg (B) | Active Moiety PK (Cmax) | 31.2 ng/mL | Geometric Coefficient of Variation 32.1 |
| LYN-005 28 mg (C) | Active Moiety PK (Cmax) | 30.4 ng/mL | Geometric Coefficient of Variation 102.7 |
| Risperidone 4 mg (A) | Active Moiety PK (Cmax) | 54.1 ng/mL | Geometric Coefficient of Variation 19.3 |
| Risperidone 4 mg (B) | Active Moiety PK (Cmax) | 46.3 ng/mL | Geometric Coefficient of Variation 23.8 |
| Risperidone 4 mg (C) | Active Moiety PK (Cmax) | 48.8 ng/mL | Geometric Coefficient of Variation 40.9 |
Primary
Active Moiety Tmax
Active Moiety Tmax (h) (risperidone and 9-hydroxyrisperidone combined) after repeat weekly doses of LYN-005 ER capsules relative to IR risperidone tablets at 2 dose levels.
Time frame: Reported data was obtained following multiple dose administration of 3 weekly doses [(IR, Day-1), (ER, Week 1), ER Week 3)] of 14 or 28 mg risperidone LYN-005 capsules to assess extended release PK.
Population: All enrolled participants who received at least 1 dose of randomized study drug and had at least 1 post-dose quantifiable (or evaluable) PK concentration data
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| LYN-005 14mg | Active Moiety Tmax | 1.9 hours |
| LYN-005 28mg | Active Moiety Tmax | 23.7 hours |
| Overall LYN-005 | Active Moiety Tmax | 23.8 hours |
| Risperidone 2 mg | Active Moiety Tmax | 3.0 hours |
| Risperidone 4 mg | Active Moiety Tmax | 1.5 hours |
| Overall Risperidone | Active Moiety Tmax | 3.0 hours |
| LYN-005 28 mg (A) | Active Moiety Tmax | 1.0 hours |
| LYN-005 28 mg (B) | Active Moiety Tmax | 24.1 hours |
| LYN-005 28 mg (C) | Active Moiety Tmax | 23.8 hours |
| Risperidone 4 mg (A) | Active Moiety Tmax | 2.1 hours |
| Risperidone 4 mg (B) | Active Moiety Tmax | 4.0 hours |
| Risperidone 4 mg (C) | Active Moiety Tmax | 2.0 hours |
Primary
Participants With at Least One Treatment Emergent Adverse Event (TEAE).
Incidence of treatment emergent adverse events (TEAEs) reported as participants with at least one treatment emergent adverse event (TEAE).
Time frame: 35 days
Population: Safety Population: All enrolled participants who were randomized to study drug (LYN-005 14 mg/28 mg or IR risperidone 2 mg/4 mg) and received at least 1 dose of randomized study drug. Participants were reported according to the treatment received. The Safety Population was the primary safety analysis population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| LYN-005 14mg | Participants With at Least One Treatment Emergent Adverse Event (TEAE). | 10 Number of Participants with TEAEs |
| LYN-005 28mg | Participants With at Least One Treatment Emergent Adverse Event (TEAE). | 8 Number of Participants with TEAEs |
| Overall LYN-005 | Participants With at Least One Treatment Emergent Adverse Event (TEAE). | 18 Number of Participants with TEAEs |
| Risperidone 2 mg | Participants With at Least One Treatment Emergent Adverse Event (TEAE). | 1 Number of Participants with TEAEs |
| Risperidone 4 mg | Participants With at Least One Treatment Emergent Adverse Event (TEAE). | 1 Number of Participants with TEAEs |
| Overall Risperidone | Participants With at Least One Treatment Emergent Adverse Event (TEAE). | 2 Number of Participants with TEAEs |
Primary
Total Number of Treatment Emergent Adverse Events (TEAEs).
Incidence of treatment emergent adverse events (TEAEs) reported as total number of TEAEs.
Time frame: 35 days
Population: Safety Population: All enrolled participants who were randomized to study drug (LYN-005 14 mg/28 mg or IR risperidone 2 mg/4 mg) and received at least 1 dose of randomized study drug. Participants were reported according to the treatment received. The Safety Population was the primary safety analysis population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| LYN-005 14mg | Total Number of Treatment Emergent Adverse Events (TEAEs). | 15 Number of Experienced TEAEs |
| LYN-005 28mg | Total Number of Treatment Emergent Adverse Events (TEAEs). | 21 Number of Experienced TEAEs |
| Overall LYN-005 | Total Number of Treatment Emergent Adverse Events (TEAEs). | 36 Number of Experienced TEAEs |
| Risperidone 2 mg | Total Number of Treatment Emergent Adverse Events (TEAEs). | 2 Number of Experienced TEAEs |
| Risperidone 4 mg | Total Number of Treatment Emergent Adverse Events (TEAEs). | 2 Number of Experienced TEAEs |
| Overall Risperidone | Total Number of Treatment Emergent Adverse Events (TEAEs). | 4 Number of Experienced TEAEs |
Secondary
PK of 9-Hydroxyrisperidone (AUC0-24h, AUC0-168h).
To characterize exposure (AUC0-24h, AUC0-168h) of 9-Hydroxyrisperidone during the switch to LYN-005.
Time frame: Reported data was obtained following multiple dose administration of 3 weekly doses [(IR, Day-1), (ER, Week 1), ER Week 3)] of 14 or 28 mg risperidone LYN-005 capsules to assess extended release PK.
Population: All enrolled participants who received at least 1 dose of randomized study drug and had at least 1 post-dose quantifiable (or evaluable) PK concentration data
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| LYN-005 14mg | PK of 9-Hydroxyrisperidone (AUC0-24h, AUC0-168h). | AUC0-24h | 315 h*ng/mL | Geometric Coefficient of Variation 39.7 |
| LYN-005 28mg | PK of 9-Hydroxyrisperidone (AUC0-24h, AUC0-168h). | AUC0-24h | 268 h*ng/mL | Geometric Coefficient of Variation 38.2 |
| LYN-005 28mg | PK of 9-Hydroxyrisperidone (AUC0-24h, AUC0-168h). | AUC0-168h | 1530 h*ng/mL | Geometric Coefficient of Variation 51.7 |
| Overall LYN-005 | PK of 9-Hydroxyrisperidone (AUC0-24h, AUC0-168h). | AUC0-168h | 1770 h*ng/mL | Geometric Coefficient of Variation 54.4 |
| Overall LYN-005 | PK of 9-Hydroxyrisperidone (AUC0-24h, AUC0-168h). | AUC0-24h | 302 h*ng/mL | Geometric Coefficient of Variation 47 |
| Risperidone 2 mg | PK of 9-Hydroxyrisperidone (AUC0-24h, AUC0-168h). | AUC0-24h | 243 h*ng/mL | Geometric Coefficient of Variation 11.2 |
| Risperidone 4 mg | PK of 9-Hydroxyrisperidone (AUC0-24h, AUC0-168h). | AUC0-24h | 262 h*ng/mL | Geometric Coefficient of Variation 20.8 |
| Overall Risperidone | PK of 9-Hydroxyrisperidone (AUC0-24h, AUC0-168h). | AUC0-24h | 265 h*ng/mL | Geometric Coefficient of Variation 26.6 |
| LYN-005 28 mg (A) | PK of 9-Hydroxyrisperidone (AUC0-24h, AUC0-168h). | AUC0-24h | 268 h*ng/mL | Geometric Coefficient of Variation 272.6 |
| LYN-005 28 mg (B) | PK of 9-Hydroxyrisperidone (AUC0-24h, AUC0-168h). | AUC0-24h | 441 h*ng/mL | Geometric Coefficient of Variation 33.6 |
| LYN-005 28 mg (B) | PK of 9-Hydroxyrisperidone (AUC0-24h, AUC0-168h). | AUC0-168h | 2720 h*ng/mL | Geometric Coefficient of Variation 35.9 |
| LYN-005 28 mg (C) | PK of 9-Hydroxyrisperidone (AUC0-24h, AUC0-168h). | AUC0-24h | 523 h*ng/mL | Geometric Coefficient of Variation 177.9 |
| LYN-005 28 mg (C) | PK of 9-Hydroxyrisperidone (AUC0-24h, AUC0-168h). | AUC0-168h | 2090 h*ng/mL | Geometric Coefficient of Variation 100.5 |
| Risperidone 4 mg (A) | PK of 9-Hydroxyrisperidone (AUC0-24h, AUC0-168h). | AUC0-24h | 641 h*ng/mL | Geometric Coefficient of Variation 43.5 |
| Risperidone 4 mg (B) | PK of 9-Hydroxyrisperidone (AUC0-24h, AUC0-168h). | AUC0-24h | 665 h*ng/mL | Geometric Coefficient of Variation 42.9 |
| Risperidone 4 mg (C) | PK of 9-Hydroxyrisperidone (AUC0-24h, AUC0-168h). | AUC0-24h | 645 h*ng/mL | Geometric Coefficient of Variation 45.5 |
Secondary
PK of 9-Hydroxyrisperidone (Cmax).
To characterize exposure (Cmax) of 9-Hydroxyrisperidone during the switch to LYN-005.
Time frame: Reported data was obtained following multiple dose administration of 3 weekly doses [(IR, Day-1), (ER, Week 1), ER Week 3)] of 14 or 28 mg risperidone LYN-005 capsules to assess extended release PK.
Population: All enrolled participants who received at least 1 dose of randomized study drug and had at least 1 post-dose quantifiable (or evaluable) PK concentration data
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| LYN-005 14mg | PK of 9-Hydroxyrisperidone (Cmax). | 20.8 ng/mL | Geometric Coefficient of Variation 31 |
| LYN-005 28mg | PK of 9-Hydroxyrisperidone (Cmax). | 16.1 ng/mL | Geometric Coefficient of Variation 49.6 |
| Overall LYN-005 | PK of 9-Hydroxyrisperidone (Cmax). | 15.6 ng/mL | Geometric Coefficient of Variation 41.9 |
| Risperidone 2 mg | PK of 9-Hydroxyrisperidone (Cmax). | 15.5 ng/mL | Geometric Coefficient of Variation 12.1 |
| Risperidone 4 mg | PK of 9-Hydroxyrisperidone (Cmax). | 17.5 ng/mL | Geometric Coefficient of Variation 37.8 |
| Overall Risperidone | PK of 9-Hydroxyrisperidone (Cmax). | 16.9 ng/mL | Geometric Coefficient of Variation 53.3 |
| LYN-005 28 mg (A) | PK of 9-Hydroxyrisperidone (Cmax). | 16.0 ng/mL | Geometric Coefficient of Variation 282.3 |
| LYN-005 28 mg (B) | PK of 9-Hydroxyrisperidone (Cmax). | 24.7 ng/mL | Geometric Coefficient of Variation 26 |
| LYN-005 28 mg (C) | PK of 9-Hydroxyrisperidone (Cmax). | 22.5 ng/mL | Geometric Coefficient of Variation 91.1 |
| Risperidone 4 mg (A) | PK of 9-Hydroxyrisperidone (Cmax). | 39.6 ng/mL | Geometric Coefficient of Variation 22.9 |
| Risperidone 4 mg (B) | PK of 9-Hydroxyrisperidone (Cmax). | 35.7 ng/mL | Geometric Coefficient of Variation 24.5 |
| Risperidone 4 mg (C) | PK of 9-Hydroxyrisperidone (Cmax). | 36.2 ng/mL | Geometric Coefficient of Variation 38.4 |
Secondary
PK of Risperidone (AUC0-24h, AUC0-168).
To characterize exposure (AUC0-24h, AUC0-168) of risperidone during the switch to LYN-005.
Time frame: Reported data was obtained following multiple dose administration of 3 weekly doses [(IR, Day-1), (ER, Week 1), ER Week 3)] of 14 or 28 mg risperidone LYN-005 capsules to assess extended release PK.
Population: All enrolled participants who received at least 1 dose of randomized study drug and had at least 1 post-dose quantifiable (or evaluable) PK concentration data
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| LYN-005 14mg | PK of Risperidone (AUC0-24h, AUC0-168). | AUC0-24h | 54.9 h*ng/mL | Geometric Coefficient of Variation 81.5 |
| LYN-005 28mg | PK of Risperidone (AUC0-24h, AUC0-168). | AUC0-24h | 65.8 h*ng/mL | Geometric Coefficient of Variation 93.3 |
| LYN-005 28mg | PK of Risperidone (AUC0-24h, AUC0-168). | AUC0-168 | 227 h*ng/mL | Geometric Coefficient of Variation 87.3 |
| Overall LYN-005 | PK of Risperidone (AUC0-24h, AUC0-168). | AUC0-168 | 306 h*ng/mL | Geometric Coefficient of Variation 67.1 |
| Overall LYN-005 | PK of Risperidone (AUC0-24h, AUC0-168). | AUC0-24h | 65.2 h*ng/mL | Geometric Coefficient of Variation 66.6 |
| Risperidone 2 mg | PK of Risperidone (AUC0-24h, AUC0-168). | AUC0-24h | 43.4 h*ng/mL | Geometric Coefficient of Variation 131.2 |
| Risperidone 4 mg | PK of Risperidone (AUC0-24h, AUC0-168). | AUC0-24h | 47.7 h*ng/mL | Geometric Coefficient of Variation 103.5 |
| Overall Risperidone | PK of Risperidone (AUC0-24h, AUC0-168). | AUC0-24h | 86.2 h*ng/mL | Geometric Coefficient of Variation 58.1 |
| LYN-005 28 mg (A) | PK of Risperidone (AUC0-24h, AUC0-168). | AUC0-24h | 113 h*ng/mL | Geometric Coefficient of Variation 109.9 |
| LYN-005 28 mg (B) | PK of Risperidone (AUC0-24h, AUC0-168). | AUC0-24h | 111 h*ng/mL | Geometric Coefficient of Variation 88.1 |
| LYN-005 28 mg (B) | PK of Risperidone (AUC0-24h, AUC0-168). | AUC0-168 | 806 h*ng/mL | Geometric Coefficient of Variation 91.2 |
| LYN-005 28 mg (C) | PK of Risperidone (AUC0-24h, AUC0-168). | AUC0-168 | 453 h*ng/mL | Geometric Coefficient of Variation 276.8 |
| LYN-005 28 mg (C) | PK of Risperidone (AUC0-24h, AUC0-168). | AUC0-24h | 119 h*ng/mL | Geometric Coefficient of Variation 257.4 |
| Risperidone 4 mg (A) | PK of Risperidone (AUC0-24h, AUC0-168). | AUC0-24h | 87.1 h*ng/mL | Geometric Coefficient of Variation 67.2 |
| Risperidone 4 mg (B) | PK of Risperidone (AUC0-24h, AUC0-168). | AUC0-24h | 82.4 h*ng/mL | Geometric Coefficient of Variation 67 |
| Risperidone 4 mg (C) | PK of Risperidone (AUC0-24h, AUC0-168). | AUC0-24h | 84.4 h*ng/mL | Geometric Coefficient of Variation 80.5 |
Secondary
PK of Risperidone (Cmax).
To characterize exposure (Cmax) of risperidone during the switch to LYN-005.
Time frame: Reported data was obtained following multiple dose administration of 3 weekly doses [(IR, Day-1), (ER, Week 1), ER Week 3)] of 14 or 28 mg risperidone LYN-005 capsules to assess extended release PK.
Population: All enrolled participants who received at least 1 dose of randomized study drug and had at least 1 post-dose quantifiable (or evaluable) PK concentration data
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| LYN-005 14mg | PK of Risperidone (Cmax). | 11.7 ng/mL | Geometric Coefficient of Variation 58.2 |
| LYN-005 28mg | PK of Risperidone (Cmax). | 4.44 ng/mL | Geometric Coefficient of Variation 95.3 |
| Overall LYN-005 | PK of Risperidone (Cmax). | 4.07 ng/mL | Geometric Coefficient of Variation 59.1 |
| Risperidone 2 mg | PK of Risperidone (Cmax). | 9.97 ng/mL | Geometric Coefficient of Variation 111 |
| Risperidone 4 mg | PK of Risperidone (Cmax). | 12.3 ng/mL | Geometric Coefficient of Variation 40.5 |
| Overall Risperidone | PK of Risperidone (Cmax). | 15.6 ng/mL | Geometric Coefficient of Variation 84.2 |
| LYN-005 28 mg (A) | PK of Risperidone (Cmax). | 21.2 ng/mL | Geometric Coefficient of Variation 55.6 |
| LYN-005 28 mg (B) | PK of Risperidone (Cmax). | 6.87 ng/mL | Geometric Coefficient of Variation 72.7 |
| LYN-005 28 mg (C) | PK of Risperidone (Cmax). | 7.39 ng/mL | Geometric Coefficient of Variation 230.9 |
| Risperidone 4 mg (A) | PK of Risperidone (Cmax). | 17.0 ng/mL | Geometric Coefficient of Variation 21.2 |
| Risperidone 4 mg (B) | PK of Risperidone (Cmax). | 13.5 ng/mL | Geometric Coefficient of Variation 32.6 |
| Risperidone 4 mg (C) | PK of Risperidone (Cmax). | 14.0 ng/mL | Geometric Coefficient of Variation 33 |