Pharmacokinetics, Safety and Tolerability of Different Formulations and Dose Strengths of Quarterly Risperidone (QUAR) in Patients With Schizophrenia

Phase 1

Recruiting

• Conditions: Schizophrenia
• Interventions: Drug: Oral risperidone; QUAR F1/2, Dose 1 - Gluteal; Drug: Oral risperidone; QUAR F1/2, Dose 2 - Gluteal; Drug: Oral risperidone; QUAR F1/2, Dose 3 - Gluteal; Drug: Oral risperidone; QUAR F1/2, Dose 3 - Deltoids

• Registration Number: NCT06276361
• Lead Sponsor: Rovi Pharmaceuticals Laboratories

Brief Summary

This is a single ascending dose phase 1 study to evaluate the pharmacokinetics (PK), safety, and tolerability of a single intramuscular (IM) injection of quarterly Risperidone (QUAR) for different formulations and dose strengths in participants with schizophrenia.

Detailed Description

The study will assess the PK, safety and tolerability of QUAR when administered as a single IM injection, in patients with schizophrenia. The study will be conducted with 3 different dose strengths and up to two formulations.

After eligibility confirmation, an oral treatment period follow by a washout period will be performed before QUAR IM administration.

The different cohorts will be administered with one of the following dosages of Risperidone QUAR:

Cohort 1/2: Formulation 1 or 2. Dose level 1 (Gluteal); Cohort 1a/2a: Formulation 1 or 2. Dose level 2 (Gluteal); Cohort 1b/2b: Formulation 1 or 2. Dose level 3 (Gluteal); Cohort 1c/2c: Formulation 1 or 2. Dose level 3 (Deltoid);

The progression to the next cohorts will take place after a clinical safety assessment. Several blood samples for plasma pharmacokinetic (PK) assessments will be obtained pre-dose and post-dose. Safety assessments will be conducted at each pre-specified time points.

After assessment of Cohort 1 (formulation 1, Dose Level 1, -gluteus-) progression to the next cohort with same formulation and escalating dose will take place (Cohort 1a -gluteus-). After assessment of Cohort 1a, progression and randomization (gluteus/deltoid) to the next cohorts with same formulation and escalating dose will take place (Cohort 1b -gluteus- and Cohort 1c -deltoid-). In this scenario, none of the Cohorts 2 will be conducted.

If the assessment for Cohort 1 is not adequate, none of the subsequent Cohorts 1 (a/b/c) will be conducted and progression to the next cohort (Cohort 2) with different formulation and same level of dose as Cohort 1 will take place (Cohort 2: Formulation 2, Dose Level 1 -gluteus-). After assessment of Cohort 2, progression to the next cohort with same formulation and escalating dose will take place (Cohort 2a -gluteus-). After assessment of Cohort 2a, progression and randomization (gluteus/deltoid) to the next cohorts with same formulation and escalating dose will take place (Cohort 2b -gluteus- and Cohort 2c -deltoid-).

Study Timeline

• Study Start: 2023-09-26
• Study First Submitted: 2024-02-16
• Study First Submitted QC: 2024-02-16
• Study First Posted: 2024-02-26
• Status Verified: 2024-07
• Last Update Submitted: 2024-07-08
• Last Update Posted: 2024-07-09
• Primary Completion: 2026-05
• Study Completion: 2026-05

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 100

Inclusion Criteria

• Capable of providing informed consent.
• Male or female aged ≥ 18 years to < 65 years with BMI ≥17.0 to ≤35.0 kg/m2
• Current diagnosis of schizophrenia, according to the Diagnostic and DSM-5 criteria.
• Medically stable over the last month, and psychiatrically stable without significant symptom exacerbation over the last three months based on the investigator's judgment
• currently taking oral risperidone as maintenance therapy
• Score of ≤ 4 (moderately ill at most) on the Clinical Global Impression - Severity of Illness (CGI-S)
• If a sexually active female of childbearing potential, using a medically accepted method of birth control.

Exclusion Criteria

• Presence of an uncontrolled, unstable, clinically significant medical condition that in the opinion of the investigator could interfere with the interpretation of safety and PK evaluations
• If female, a positive serum pregnancy test, or planning to become pregnant between signing informed consent and 1 month after the last dose of study drug or is breastfeeding a child.
• History of neuroleptic malignant syndrome and current or past history of clinically significant tardive dyskinesia.
• The participant has a primary diagnosis other than schizophrenia diagnosis that is primarily responsible for current symptoms and functional impairment
• Positive test result for drugs of abuse or alcohol unless the positive finding can be accounted for by documented prescription use.
• In the investigator's opinion, at imminent risk of committing self-harm or harm to others.
• Unwilling to discontinue any of the prohibited medications prior to the baseline visit or unable to safely washout such medication without significant destabilization or increased risk of self-harm (suicide).
• Receipt study drug in another investigational study in the last 90 days.
• Current participation in any other clinical trial.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Cohort 1/2	Oral risperidone; QUAR F1/2, Dose 1 - Gluteal	Patient will recieve oral risperidone for one week followed by a single IM injection of Risperidone QUAR out of two possible formulations (F1/F2) with a level 1 dose.
Cohort 1a/2a	Oral risperidone; QUAR F1/2, Dose 2 - Gluteal	Patient will recieve oral risperidone for one week followed by a single IM injection of Risperidone QUAR out of two possible formulations (F1/F2) with a level 2 dose.
Cohort 1b//2b	Oral risperidone; QUAR F1/2, Dose 3 - Gluteal	Patient will recieve oral risperidone for one week followed by a single IM injection of Risperidone QUAR out of two possible formulations (F1/F2) with a level 3 dose.
Cohort 1c/2c	Oral risperidone; QUAR F1/2, Dose 3 - Deltoids	Patient will recieve oral risperidone for one week followed by a single IM injection of Risperidone QUAR out of two possible formulations (F1/F2) with a level 3 dose.

Primary Outcome Measures

Name	Time	Method
λz	Following Oral and QUAR administration until day 17 or 196 respectively	Terminal elimination rate constant
t1/2	Following Oral and QUAR administration until day 17 or 196 respectively	Terminal elimination half-life
Cmax	Following Oral and QUAR administration until day 17 or 196 respectively	Peak plasma concentration
Tmax	Following Oral and QUAR administration until day 17 or 196 respectively	Time to peak concentration
Cmin	Following Oral and QUAR administration until day 17 or 196 respectively	Minimum plasma concentration
Clast	Following Oral and QUAR administration until day 17 or 196 respectively	Last observed plasma concentration
AUC0-t	Following Oral and QUAR administration until day 17 or 196 respectively	Area under the curve
AUCinf	Following QUAR administration until day 196	Area under the curve
AUCextrap	Following QUAR administration until day 196	Area under the curve
Vd/F	Following Oral and QUAR administration until day 17 or 196 respectively	Apparent volume of distribution
Cl/F	Following Oral and QUAR administration until day 17 or 196 respectively	Apparent total body clearance

Trial Locations

Locations (1)

Investigational Site; 🇯🇴 Amman, Jordan