Safety, Tolerability, and Pharmacokinetics of Iloperidone Depot in Schizophrenic Patients

Schizophrenia Clinical Trial

Official title:

An Open-label Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of Two Iloperidone Depot Formulations Followed by a Dose-ranging Phase of One Selected Formulation in Schizophrenic Patients Given Depot Injections Every 28 Days

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01348100
• Other study ID #: CILO522E2101
• Status: Completed
• Phase: Phase 1/Phase 2
• First received: April 28, 2011
• Last updated: December 17, 2013
• Start date: April 2011
• Est. completion date: July 2012

Study information

• Verified date: December 2013
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 81
• Est. completion date: July 2012
• Est. primary completion date: July 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 65 Years

Eligibility

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/exclusion criteria may apply.

Study Design

Allocation: Randomized, Endpoint Classification: Pharmacokinetics Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Schizophrenia

Intervention

Drug:
• Iloperidone crystalline formulation
Iloperidone was formulated as 100 µm crystals for IM depot injection.
• Iloperidone microparticle formulation
Iloperidone was formulated as microparticles for IM depot injection.
• Oral 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.

Locations

Country	Name	City	State
United States	Novartis Investigative Site	Glendale	California
United States	Novartis Investigative Site	Philadelphia	Pennsylvania

Sponsors (2)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals	Vanda Pharmaceuticals

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
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.	Pre-dose to 26 days post-dose	No
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.	Pre-dose to 26 days post-dose	No
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.	Pre-dose to 26 days post-dose	No
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.	Pre-dose to 26 days post-dose	No
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).	Pre-dose to 26 days post-dose	No
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.	Pre-dose to 26 days post-dose	No
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.	Pre-dose to 26 days post-dose	No
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.	Pre-dose to 26 days post-dose	No
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.	Pre-dose to 26 days post-dose	No
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.	Pre-dose to 26 days post-dose	No
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).	Pre-dose to 26 days post-dose	No
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.	Pre-dose to 26 days post-dose	No