Schizophrenia
Conditions
Keywords
Schizophrenia, Iloperidone, Depot, Injection
Brief summary
This study is designed as a 3-part trial to evaluate the safety of a novel depot formulation of iloperidone, compare 2 depot dosage forms, and perform dose ranging of 1 chosen form in support of a monthly depot dosing regimen. In Phase A, the study is designed to evaluate the safety of a crystalline iloperidone depot formulation. In Phase B, the pharmacokinetic and safety profile of 2 depot clinical dosage forms will be compared, and 1 form will be selected for assessment in Phase C. Phase C of this study is designed to define the dose-exposure relationship of the selected form and to provide information that will permit a comparison of the risk-benefit ratio of several doses of the study drug to enable optimal dose selection for later studies.
Interventions
DRUGIloperidone crystalline formulation
Iloperidone was formulated as 100 µm crystals for IM depot injection.
DRUGIloperidone microparticle formulation
Iloperidone was formulated as microparticles for IM depot injection.
DRUGOral iloperidone
Prior to receiving an intramuscular (IM) injection of iloperidone, patients were gradually titrated up with oral iloperidone to stable doses of 12 to 24 mg daily. In Phase A, oral iloperidone dosing lasted for at least 7 days and, in Phases B and C, for at least 10 to 14 days.
Sponsors
Vanda Pharmaceuticals
Novartis Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Patients with schizophrenia that have been stable for 3 months.
Exclusion criteria
* Women who can become or are currently pregnant or lactating. * Hypersensitivity to iloperidone or related drugs. Other protocol-defined inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Observed Plasma Concentration (Cmax) of Iloperidone Divided by the Average Plasma Concentration (Cav) of Iloperidone (Cmax/Cav) - Phase B | Pre-dose to 26 days post-dose | Blood samples for pharmacokinetic (PK) evaluation were drawn pre-dose and at 3, 6, and 12 hours on Day 1; at 0 and 12 hours on Day 2; and on Days 3, 4, 6, 8, 10, 14, 18, 22, and 26 following administration of iloperidone. PK parameters were calculated from plasma concentration-time data using non-compartmental methods. |
| The Average Plasma Concentration (Cav) of Iloperidone - Phase C | Pre-dose to 26 days post-dose | Blood samples for pharmacokinetic (PK) evaluation were drawn pre-dose and at 3, 6, and 12 hours on Day 1; at 0 and 12 hours on Day 2; and on Days 3, 4, 6, 8, 10, 14, 18, 22, and 26 following administration of iloperidone. Blood samples were collected after each depot injection. PK parameters were calculated from plasma concentration-time data using non-compartmental methods. Cav was calculated as AUC0-672h/672 h. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to Reach the Maximum Plasma Concentration (Tmax) of Iloperidone - Phase B | Pre-dose to 26 days post-dose | Blood samples for pharmacokinetic (PK) evaluation were drawn pre-dose and at 3, 6, and 12 hours on Day 1; at 0 and 12 hours on Day 2; and on Days 3, 4, 6, 8, 10, 14, 18, 22, and 26 following administration of iloperidone. PK parameters were calculated from plasma concentration-time data using non-compartmental methods. |
| Maximum Observed Plasma Concentration (Cmax) of Iloperidone - Phase B | Pre-dose to 26 days post-dose | Blood samples for pharmacokinetic (PK) evaluation were drawn pre-dose and at 3, 6, and 12 hours on Day 1; at 0 and 12 hours on Day 2; and on Days 3, 4, 6, 8, 10, 14, 18, 22, and 26 following administration of iloperidone. PK parameters were calculated from plasma concentration-time data using non-compartmental methods. |
| Area Under the Plasma Concentration-time Curve From 0 to the End of the Dosing Period (AUCtau) of Iloperidone - Phase B | Pre-dose to 26 days post-dose | Blood samples for pharmacokinetic (PK) evaluation were drawn pre-dose and at 3, 6, and 12 hours on Day 1; at 0 and 12 hours on Day 2; and on Days 3, 4, 6, 8, 10, 14, 18, 22, and 26 following administration of iloperidone. PK parameters were calculated from plasma concentration-time data using non-compartmental methods. The area under the curve was calculated using a linear trapezoidal method. The end of the dosing period was 672 hours (28 days). |
| Area Under the Plasma Concentration-time Curve From 0 to the Last Measurable Concentration (AUClast) of Iloperidone - Phase B | Pre-dose to 26 days post-dose | Blood samples for pharmacokinetic (PK) evaluation were drawn pre-dose and at 3, 6, and 12 hours on Day 1; at 0 and 12 hours on Day 2; and on Days 3, 4, 6, 8, 10, 14, 18, 22, and 26 following administration of iloperidone. PK parameters were calculated from plasma concentration-time data using non-compartmental methods. The area under the curve was calculated using a linear trapezoidal method. |
| The Average Plasma Concentration (Cav) of Iloperidone - Phase B | Pre-dose to 26 days post-dose | Blood samples for pharmacokinetic (PK) evaluation were drawn pre-dose and at 3, 6, and 12 hours on Day 1; at 0 and 12 hours on Day 2; and on Days 3, 4, 6, 8, 10, 14, 18, 22, and 26 following administration of iloperidone. PK parameters were calculated from plasma concentration-time data using non-compartmental methods. Cav was calculated as AUC0-672h/672 h. |
| Duration That the Concentration of Iloperidone Was Above 4 ng/mL (Teff) - Phase B | Pre-dose to 26 days post-dose | Blood samples for pharmacokinetic (PK) evaluation were drawn pre-dose and at 3, 6, and 12 hours on Day 1; at 0 and 12 hours on Day 2; and on Days 3, 4, 6, 8, 10, 14, 18, 22, and 26 following administration of iloperidone. PK parameters were calculated from plasma concentration-time data using non-compartmental methods. The duration that the concentration of iloperidone was above 4 ng/mL was calculated by linear interpolation. PK/pharmacodynamic analysis performed in other studies suggests that iloperidone plasma levels of 4 ng/mL or above provide clinical efficacy. |
| Time to Reach the Maximum Plasma Concentration (Tmax) of Iloperidone - Phase C | Pre-dose to 26 days post-dose | Blood samples for pharmacokinetic (PK) evaluation were drawn pre-dose and at 3, 6, and 12 hours on Day 1; at 0 and 12 hours on Day 2; and on Days 3, 4, 6, 8, 10, 14, 18, 22, and 26 following administration of iloperidone. Blood samples were collected after each depot injection. PK parameters were calculated from plasma concentration-time data using non-compartmental methods. |
| Maximum Observed Plasma Concentration (Cmax) of Iloperidone - Phase C | Pre-dose to 26 days post-dose | Blood samples for pharmacokinetic (PK) evaluation were drawn pre-dose and at 3, 6, and 12 hours on Day 1; at 0 and 12 hours on Day 2; and on Days 3, 4, 6, 8, 10, 14, 18, 22, and 26 following administration of iloperidone. Blood samples were collected after each depot injection. PK parameters were calculated from plasma concentration-time data using non-compartmental methods. |
| Area Under the Plasma Concentration-time Curve From 0 to the End of the Dosing Period (AUCtau) of Iloperidone - Phase C | Pre-dose to 26 days post-dose | Blood samples for pharmacokinetic (PK) evaluation were drawn pre-dose and at 3, 6, and 12 hours on Day 1; at 0 and 12 hours on Day 2; and on Days 3, 4, 6, 8, 10, 14, 18, 22, and 26 following administration of iloperidone. Blood samples were collected after each depot injection. PK parameters were calculated from plasma concentration-time data using non-compartmental methods. The area under the curve was calculated using a linear trapezoidal method. The end of the dosing period was 672 hours (28 days). |
| The Average Plasma Concentration (Cav) of Iloperidone Divided by Dose - Phase C | Pre-dose to 26 days post-dose | Blood samples for pharmacokinetic (PK) evaluation were drawn pre-dose and at 3, 6, and 12 hours on Day 1; at 0 and 12 hours on Day 2; and on Days 3, 4, 6, 8, 10, 14, 18, 22, and 26 following administration of iloperidone. Blood samples were collected after each depot injection. PK parameters were calculated from plasma concentration-time data using non-compartmental methods. Cav was calculated as AUC0-672h/672 h. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Iloperidone 50 mg Crystalline Formulation - Phase A Participants received a crystalline formulation of iloperidone 50 mg in a depot intramuscular (IM) injection 1 time. Prior to receiving IM iloperidone, participants were gradually titrated up with oral iloperidone for at least 7 days to stable doses of 12 to 24 mg daily. | 2 |
| Iloperidone 125 mg Crystalline Formulation - Phase A Participants received a crystalline formulation of iloperidone 125 mg in a depot IM injection 1 time. Prior to receiving IM iloperidone, participants were gradually titrated up with oral iloperidone for at least 7 days to stable doses of 12 to 24 mg daily. | 2 |
| Iloperidone 250 mg Crystalline Formulation - Phase B Participants received a crystalline formulation of iloperidone 250 mg in a depot IM injection 1 time. Prior to receiving IM iloperidone, participants were gradually titrated up with oral iloperidone for at least 10 to 14 days to stable doses of 12 to 24 mg daily. | 15 |
| Iloperidone 250 mg Microparticle Formulation - Phase B Participants received a microparticle formulation of iloperidone 250 mg in a depot IM injection 1 time. Prior to receiving IM iloperidone, participants were gradually titrated up with oral iloperidone for at least 10 to 14 days to stable doses of 12 to 24 mg daily. | 15 |
| Iloperidone 250 mg Microparticle Formulation - Phase C Participants received a microparticle formulation of iloperidone 250 mg in a depot IM injection 2 times 28 days apart. Prior to receiving IM iloperidone, participants were gradually titrated up with oral iloperidone for at least 10 to 14 days to stable doses of 12 to 24 mg daily. | 15 |
| Iloperidone 500 mg Microparticle Formulation - Phase C Participants received a microparticle formulation of iloperidone 500 mg in a depot IM injection 2 times 28 days apart. Prior to receiving IM iloperidone, participants were gradually titrated up with oral iloperidone for at least 10 to 14 days to stable doses of 12 to 24 mg daily. | 16 |
| Iloperidone 625 mg Microparticle Formulation - Phase C Participants received a microparticle formulation of iloperidone 625 mg in a depot IM injection 2 times 28 days apart. Prior to receiving IM iloperidone, participants were gradually titrated up with oral iloperidone for at least 10 to 14 days to stable doses of 12 to 24 mg daily. | 16 |
| Total | 81 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 |
|---|---|---|---|---|---|---|---|---|
| Overall Study | Administrative Problems | 0 | 0 | 0 | 0 | 0 | 1 | 1 |
| Overall Study | Lost to Follow-up | 0 | 0 | 0 | 0 | 0 | 0 | 1 |
| Overall Study | Protocol Deviation | 0 | 0 | 0 | 1 | 0 | 0 | 0 |
| Overall Study | Subject Withdrew Consent | 0 | 0 | 2 | 0 | 1 | 0 | 1 |
| Overall Study | Unsatisfactory Therapeutic Effect | 0 | 0 | 0 | 0 | 0 | 1 | 0 |
Baseline characteristics
| Characteristic | Iloperidone 50 mg Crystalline Formulation - Phase A | Iloperidone 125 mg Crystalline Formulation - Phase A | Iloperidone 250 mg Crystalline Formulation - Phase B | Iloperidone 250 mg Microparticle Formulation - Phase B | Iloperidone 250 mg Microparticle Formulation - Phase C | Iloperidone 500 mg Microparticle Formulation - Phase C | Iloperidone 625 mg Microparticle Formulation - Phase C | Total |
|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 42.0 years STANDARD_DEVIATION 2.83 | 35.5 years STANDARD_DEVIATION 12.02 | 45.5 years STANDARD_DEVIATION 14.81 | 43.5 years STANDARD_DEVIATION 13.02 | 42.3 years STANDARD_DEVIATION 10.62 | 41.3 years STANDARD_DEVIATION 10.03 | 45.1 years STANDARD_DEVIATION 11.21 | 43.3 years STANDARD_DEVIATION 11.6 |
| Sex: Female, Male Female | 0 Participants | 2 Participants | 5 Participants | 4 Participants | 6 Participants | 5 Participants | 3 Participants | 25 Participants |
| Sex: Female, Male Male | 2 Participants | 0 Participants | 10 Participants | 11 Participants | 9 Participants | 11 Participants | 13 Participants | 56 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk | EG009 affected / at risk | EG010 affected / at risk | EG011 affected / at risk | EG012 affected / at risk | EG013 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 2 / 2 | 1 / 2 | 1 / 2 | 2 / 2 | 9 / 15 | 10 / 15 | 4 / 14 | 8 / 14 | 11 / 15 | 9 / 15 | 9 / 15 | 13 / 15 | 12 / 15 | 13 / 15 |
| serious Total, serious adverse events | 0 / 2 | 0 / 2 | 0 / 2 | 0 / 2 | 0 / 15 | 0 / 15 | 2 / 14 | 1 / 14 | 0 / 15 | 0 / 15 | 0 / 15 | 0 / 15 | 0 / 15 | 0 / 15 |
Outcome results
Primary
Maximum Observed Plasma Concentration (Cmax) of Iloperidone Divided by the Average Plasma Concentration (Cav) of Iloperidone (Cmax/Cav) - Phase B
Blood samples for pharmacokinetic (PK) evaluation were drawn pre-dose and at 3, 6, and 12 hours on Day 1; at 0 and 12 hours on Day 2; and on Days 3, 4, 6, 8, 10, 14, 18, 22, and 26 following administration of iloperidone. PK parameters were calculated from plasma concentration-time data using non-compartmental methods.
Time frame: Pre-dose to 26 days post-dose
Population: Pharmacokinetic population: All participants with evaluable pharmacokinetic data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Iloperidone 250 mg Crystalline Formulation - Phase B | Maximum Observed Plasma Concentration (Cmax) of Iloperidone Divided by the Average Plasma Concentration (Cav) of Iloperidone (Cmax/Cav) - Phase B | 1.91 Ratio of Cmax to Cav | Standard Deviation 0.513 |
| Iloperidone 250 mg Microparticle Formulation - Phase B | Maximum Observed Plasma Concentration (Cmax) of Iloperidone Divided by the Average Plasma Concentration (Cav) of Iloperidone (Cmax/Cav) - Phase B | 1.87 Ratio of Cmax to Cav | Standard Deviation 0.554 |
Primary
The Average Plasma Concentration (Cav) of Iloperidone - Phase C
Blood samples for pharmacokinetic (PK) evaluation were drawn pre-dose and at 3, 6, and 12 hours on Day 1; at 0 and 12 hours on Day 2; and on Days 3, 4, 6, 8, 10, 14, 18, 22, and 26 following administration of iloperidone. Blood samples were collected after each depot injection. PK parameters were calculated from plasma concentration-time data using non-compartmental methods. Cav was calculated as AUC0-672h/672 h.
Time frame: Pre-dose to 26 days post-dose
Population: Pharmacokinetic population: All participants with evaluable pharmacokinetic data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Iloperidone 250 mg Crystalline Formulation - Phase B | The Average Plasma Concentration (Cav) of Iloperidone - Phase C | Dose 1 - n = 15, 13, 12 | 3.73 ng/mL | Standard Deviation 1.16 |
| Iloperidone 250 mg Crystalline Formulation - Phase B | The Average Plasma Concentration (Cav) of Iloperidone - Phase C | Dose 2 - n = 14, 14, 13 | 4.52 ng/mL | Standard Deviation 1.5 |
| Iloperidone 250 mg Microparticle Formulation - Phase B | The Average Plasma Concentration (Cav) of Iloperidone - Phase C | Dose 1 - n = 15, 13, 12 | 7.93 ng/mL | Standard Deviation 5.29 |
| Iloperidone 250 mg Microparticle Formulation - Phase B | The Average Plasma Concentration (Cav) of Iloperidone - Phase C | Dose 2 - n = 14, 14, 13 | 10.1 ng/mL | Standard Deviation 5.46 |
| Iloperidone 625 mg Microparticle Formulation - Phase C | The Average Plasma Concentration (Cav) of Iloperidone - Phase C | Dose 1 - n = 15, 13, 12 | 11.8 ng/mL | Standard Deviation 8.1 |
| Iloperidone 625 mg Microparticle Formulation - Phase C | The Average Plasma Concentration (Cav) of Iloperidone - Phase C | Dose 2 - n = 14, 14, 13 | 16.0 ng/mL | Standard Deviation 7.12 |
Secondary
Area Under the Plasma Concentration-time Curve From 0 to the End of the Dosing Period (AUCtau) of Iloperidone - Phase B
Blood samples for pharmacokinetic (PK) evaluation were drawn pre-dose and at 3, 6, and 12 hours on Day 1; at 0 and 12 hours on Day 2; and on Days 3, 4, 6, 8, 10, 14, 18, 22, and 26 following administration of iloperidone. PK parameters were calculated from plasma concentration-time data using non-compartmental methods. The area under the curve was calculated using a linear trapezoidal method. The end of the dosing period was 672 hours (28 days).
Time frame: Pre-dose to 26 days post-dose
Population: Pharmacokinetic population: All participants with evaluable pharmacokinetic data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Iloperidone 250 mg Crystalline Formulation - Phase B | Area Under the Plasma Concentration-time Curve From 0 to the End of the Dosing Period (AUCtau) of Iloperidone - Phase B | 2310 ng*h/mL | Standard Deviation 1170 |
| Iloperidone 250 mg Microparticle Formulation - Phase B | Area Under the Plasma Concentration-time Curve From 0 to the End of the Dosing Period (AUCtau) of Iloperidone - Phase B | 3190 ng*h/mL | Standard Deviation 1670 |
Secondary
Area Under the Plasma Concentration-time Curve From 0 to the End of the Dosing Period (AUCtau) of Iloperidone - Phase C
Blood samples for pharmacokinetic (PK) evaluation were drawn pre-dose and at 3, 6, and 12 hours on Day 1; at 0 and 12 hours on Day 2; and on Days 3, 4, 6, 8, 10, 14, 18, 22, and 26 following administration of iloperidone. Blood samples were collected after each depot injection. PK parameters were calculated from plasma concentration-time data using non-compartmental methods. The area under the curve was calculated using a linear trapezoidal method. The end of the dosing period was 672 hours (28 days).
Time frame: Pre-dose to 26 days post-dose
Population: Pharmacokinetic population: All participants with evaluable pharmacokinetic data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Iloperidone 250 mg Crystalline Formulation - Phase B | Area Under the Plasma Concentration-time Curve From 0 to the End of the Dosing Period (AUCtau) of Iloperidone - Phase C | Dose 1 - n = 15, 13, 12 | 2500 ng*h/mL | Standard Deviation 780 |
| Iloperidone 250 mg Crystalline Formulation - Phase B | Area Under the Plasma Concentration-time Curve From 0 to the End of the Dosing Period (AUCtau) of Iloperidone - Phase C | Dose 2 - n = 14, 14, 13 | 3040 ng*h/mL | Standard Deviation 1010 |
| Iloperidone 250 mg Microparticle Formulation - Phase B | Area Under the Plasma Concentration-time Curve From 0 to the End of the Dosing Period (AUCtau) of Iloperidone - Phase C | Dose 1 - n = 15, 13, 12 | 5330 ng*h/mL | Standard Deviation 3560 |
| Iloperidone 250 mg Microparticle Formulation - Phase B | Area Under the Plasma Concentration-time Curve From 0 to the End of the Dosing Period (AUCtau) of Iloperidone - Phase C | Dose 2 - n = 14, 14, 13 | 6820 ng*h/mL | Standard Deviation 3670 |
| Iloperidone 625 mg Microparticle Formulation - Phase C | Area Under the Plasma Concentration-time Curve From 0 to the End of the Dosing Period (AUCtau) of Iloperidone - Phase C | Dose 1 - n = 15, 13, 12 | 7930 ng*h/mL | Standard Deviation 5440 |
| Iloperidone 625 mg Microparticle Formulation - Phase C | Area Under the Plasma Concentration-time Curve From 0 to the End of the Dosing Period (AUCtau) of Iloperidone - Phase C | Dose 2 - n = 14, 14, 13 | 10700 ng*h/mL | Standard Deviation 4790 |
Secondary
Area Under the Plasma Concentration-time Curve From 0 to the Last Measurable Concentration (AUClast) of Iloperidone - Phase B
Blood samples for pharmacokinetic (PK) evaluation were drawn pre-dose and at 3, 6, and 12 hours on Day 1; at 0 and 12 hours on Day 2; and on Days 3, 4, 6, 8, 10, 14, 18, 22, and 26 following administration of iloperidone. PK parameters were calculated from plasma concentration-time data using non-compartmental methods. The area under the curve was calculated using a linear trapezoidal method.
Time frame: Pre-dose to 26 days post-dose
Population: Pharmacokinetic population: All participants with evaluable pharmacokinetic data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Iloperidone 250 mg Crystalline Formulation - Phase B | Area Under the Plasma Concentration-time Curve From 0 to the Last Measurable Concentration (AUClast) of Iloperidone - Phase B | 2890 ng*h/mL | Standard Deviation 1380 |
| Iloperidone 250 mg Microparticle Formulation - Phase B | Area Under the Plasma Concentration-time Curve From 0 to the Last Measurable Concentration (AUClast) of Iloperidone - Phase B | 3730 ng*h/mL | Standard Deviation 1730 |
Secondary
Duration That the Concentration of Iloperidone Was Above 4 ng/mL (Teff) - Phase B
Blood samples for pharmacokinetic (PK) evaluation were drawn pre-dose and at 3, 6, and 12 hours on Day 1; at 0 and 12 hours on Day 2; and on Days 3, 4, 6, 8, 10, 14, 18, 22, and 26 following administration of iloperidone. PK parameters were calculated from plasma concentration-time data using non-compartmental methods. The duration that the concentration of iloperidone was above 4 ng/mL was calculated by linear interpolation. PK/pharmacodynamic analysis performed in other studies suggests that iloperidone plasma levels of 4 ng/mL or above provide clinical efficacy.
Time frame: Pre-dose to 26 days post-dose
Population: Pharmacokinetic population: All participants with evaluable pharmacokinetic data.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Iloperidone 250 mg Crystalline Formulation - Phase B | Duration That the Concentration of Iloperidone Was Above 4 ng/mL (Teff) - Phase B | 150 hours |
| Iloperidone 250 mg Microparticle Formulation - Phase B | Duration That the Concentration of Iloperidone Was Above 4 ng/mL (Teff) - Phase B | 365 hours |
Secondary
Maximum Observed Plasma Concentration (Cmax) of Iloperidone - Phase B
Blood samples for pharmacokinetic (PK) evaluation were drawn pre-dose and at 3, 6, and 12 hours on Day 1; at 0 and 12 hours on Day 2; and on Days 3, 4, 6, 8, 10, 14, 18, 22, and 26 following administration of iloperidone. PK parameters were calculated from plasma concentration-time data using non-compartmental methods.
Time frame: Pre-dose to 26 days post-dose
Population: Pharmacokinetic population: All participants with evaluable pharmacokinetic data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Iloperidone 250 mg Crystalline Formulation - Phase B | Maximum Observed Plasma Concentration (Cmax) of Iloperidone - Phase B | 6.25 ng/mL | Standard Deviation 2.98 |
| Iloperidone 250 mg Microparticle Formulation - Phase B | Maximum Observed Plasma Concentration (Cmax) of Iloperidone - Phase B | 8.40 ng/mL | Standard Deviation 3.49 |
Secondary
Maximum Observed Plasma Concentration (Cmax) of Iloperidone - Phase C
Blood samples for pharmacokinetic (PK) evaluation were drawn pre-dose and at 3, 6, and 12 hours on Day 1; at 0 and 12 hours on Day 2; and on Days 3, 4, 6, 8, 10, 14, 18, 22, and 26 following administration of iloperidone. Blood samples were collected after each depot injection. PK parameters were calculated from plasma concentration-time data using non-compartmental methods.
Time frame: Pre-dose to 26 days post-dose
Population: Pharmacokinetic population: All participants with evaluable pharmacokinetic data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Iloperidone 250 mg Crystalline Formulation - Phase B | Maximum Observed Plasma Concentration (Cmax) of Iloperidone - Phase C | Dose 1 - n = 15, 14, 14 | 6.45 ng/mL | Standard Deviation 2.29 |
| Iloperidone 250 mg Crystalline Formulation - Phase B | Maximum Observed Plasma Concentration (Cmax) of Iloperidone - Phase C | Dose 2 - n = 14, 14, 13 | 8.15 ng/mL | Standard Deviation 2.98 |
| Iloperidone 250 mg Microparticle Formulation - Phase B | Maximum Observed Plasma Concentration (Cmax) of Iloperidone - Phase C | Dose 1 - n = 15, 14, 14 | 15.2 ng/mL | Standard Deviation 13.9 |
| Iloperidone 250 mg Microparticle Formulation - Phase B | Maximum Observed Plasma Concentration (Cmax) of Iloperidone - Phase C | Dose 2 - n = 14, 14, 13 | 21.6 ng/mL | Standard Deviation 19.6 |
| Iloperidone 625 mg Microparticle Formulation - Phase C | Maximum Observed Plasma Concentration (Cmax) of Iloperidone - Phase C | Dose 1 - n = 15, 14, 14 | 19.7 ng/mL | Standard Deviation 15.8 |
| Iloperidone 625 mg Microparticle Formulation - Phase C | Maximum Observed Plasma Concentration (Cmax) of Iloperidone - Phase C | Dose 2 - n = 14, 14, 13 | 29.2 ng/mL | Standard Deviation 16.4 |
Secondary
The Average Plasma Concentration (Cav) of Iloperidone Divided by Dose - Phase C
Blood samples for pharmacokinetic (PK) evaluation were drawn pre-dose and at 3, 6, and 12 hours on Day 1; at 0 and 12 hours on Day 2; and on Days 3, 4, 6, 8, 10, 14, 18, 22, and 26 following administration of iloperidone. Blood samples were collected after each depot injection. PK parameters were calculated from plasma concentration-time data using non-compartmental methods. Cav was calculated as AUC0-672h/672 h.
Time frame: Pre-dose to 26 days post-dose
Population: Pharmacokinetic population: All participants with evaluable pharmacokinetic data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Iloperidone 250 mg Crystalline Formulation - Phase B | The Average Plasma Concentration (Cav) of Iloperidone Divided by Dose - Phase C | Dose 1 - n = 15, 13, 12 | 0.0156 ng/mL/mg | Standard Deviation 0.00464 |
| Iloperidone 250 mg Crystalline Formulation - Phase B | The Average Plasma Concentration (Cav) of Iloperidone Divided by Dose - Phase C | Dose 2 - n = 14, 14, 13 | 0.0300 ng/mL/mg | Standard Deviation 0.0235 |
| Iloperidone 250 mg Microparticle Formulation - Phase B | The Average Plasma Concentration (Cav) of Iloperidone Divided by Dose - Phase C | Dose 1 - n = 15, 13, 12 | 0.0172 ng/mL/mg | Standard Deviation 0.0107 |
| Iloperidone 250 mg Microparticle Formulation - Phase B | The Average Plasma Concentration (Cav) of Iloperidone Divided by Dose - Phase C | Dose 2 - n = 14, 14, 13 | 0.0242 ng/mL/mg | Standard Deviation 0.0129 |
| Iloperidone 625 mg Microparticle Formulation - Phase C | The Average Plasma Concentration (Cav) of Iloperidone Divided by Dose - Phase C | Dose 1 - n = 15, 13, 12 | 0.0196 ng/mL/mg | Standard Deviation 0.0125 |
| Iloperidone 625 mg Microparticle Formulation - Phase C | The Average Plasma Concentration (Cav) of Iloperidone Divided by Dose - Phase C | Dose 2 - n = 14, 14, 13 | 0.0328 ng/mL/mg | Standard Deviation 0.0141 |
Secondary
The Average Plasma Concentration (Cav) of Iloperidone - Phase B
Blood samples for pharmacokinetic (PK) evaluation were drawn pre-dose and at 3, 6, and 12 hours on Day 1; at 0 and 12 hours on Day 2; and on Days 3, 4, 6, 8, 10, 14, 18, 22, and 26 following administration of iloperidone. PK parameters were calculated from plasma concentration-time data using non-compartmental methods. Cav was calculated as AUC0-672h/672 h.
Time frame: Pre-dose to 26 days post-dose
Population: Pharmacokinetic population: All participants with evaluable pharmacokinetic data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Iloperidone 250 mg Crystalline Formulation - Phase B | The Average Plasma Concentration (Cav) of Iloperidone - Phase B | 3.44 ng/mL | Standard Deviation 1.74 |
| Iloperidone 250 mg Microparticle Formulation - Phase B | The Average Plasma Concentration (Cav) of Iloperidone - Phase B | 4.74 ng/mL | Standard Deviation 2.49 |
Secondary
Time to Reach the Maximum Plasma Concentration (Tmax) of Iloperidone - Phase B
Blood samples for pharmacokinetic (PK) evaluation were drawn pre-dose and at 3, 6, and 12 hours on Day 1; at 0 and 12 hours on Day 2; and on Days 3, 4, 6, 8, 10, 14, 18, 22, and 26 following administration of iloperidone. PK parameters were calculated from plasma concentration-time data using non-compartmental methods.
Time frame: Pre-dose to 26 days post-dose
Population: Pharmacokinetic population: All participants with evaluable pharmacokinetic data.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Iloperidone 250 mg Crystalline Formulation - Phase B | Time to Reach the Maximum Plasma Concentration (Tmax) of Iloperidone - Phase B | 48.1 hours |
| Iloperidone 250 mg Microparticle Formulation - Phase B | Time to Reach the Maximum Plasma Concentration (Tmax) of Iloperidone - Phase B | 168 hours |
Secondary
Time to Reach the Maximum Plasma Concentration (Tmax) of Iloperidone - Phase C
Blood samples for pharmacokinetic (PK) evaluation were drawn pre-dose and at 3, 6, and 12 hours on Day 1; at 0 and 12 hours on Day 2; and on Days 3, 4, 6, 8, 10, 14, 18, 22, and 26 following administration of iloperidone. Blood samples were collected after each depot injection. PK parameters were calculated from plasma concentration-time data using non-compartmental methods.
Time frame: Pre-dose to 26 days post-dose
Population: Pharmacokinetic population: All participants with evaluable pharmacokinetic data.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Iloperidone 250 mg Crystalline Formulation - Phase B | Time to Reach the Maximum Plasma Concentration (Tmax) of Iloperidone - Phase C | Dose 1 - n = 15, 14, 14 | 48 hours |
| Iloperidone 250 mg Crystalline Formulation - Phase B | Time to Reach the Maximum Plasma Concentration (Tmax) of Iloperidone - Phase C | Dose 2 - n = 14, 14, 13 | 48 hours |
| Iloperidone 250 mg Microparticle Formulation - Phase B | Time to Reach the Maximum Plasma Concentration (Tmax) of Iloperidone - Phase C | Dose 1 - n = 15, 14, 14 | 227 hours |
| Iloperidone 250 mg Microparticle Formulation - Phase B | Time to Reach the Maximum Plasma Concentration (Tmax) of Iloperidone - Phase C | Dose 2 - n = 14, 14, 13 | 207 hours |
| Iloperidone 625 mg Microparticle Formulation - Phase C | Time to Reach the Maximum Plasma Concentration (Tmax) of Iloperidone - Phase C | Dose 1 - n = 15, 14, 14 | 192 hours |
| Iloperidone 625 mg Microparticle Formulation - Phase C | Time to Reach the Maximum Plasma Concentration (Tmax) of Iloperidone - Phase C | Dose 2 - n = 14, 14, 13 | 195 hours |