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

A Single Ascending Dose Phase 1 Study to Evaluate the Pharmacokinetics, Safety and Tolerability of a Single Intramuscular Injection of Quarterly Risperidone (QUAR) for Different Formulations and Dose Strengths in Participants With Schizophrenia (QUARTZ Study)

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.

Study Overview

• Status: Recruiting
• Conditions: Schizophrenia
• Intervention / Treatment: 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

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 Type: Interventional
• Enrollment (Estimated): 100
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Clinical Operations Laboratorios farmacéuticos ROVI; Phone Number: +34913756230; Email: departamento.medico@rovi.es

Study Locations

• Jordan
  • Amman, Jordan
    • Recruiting
    • Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1/2; 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.	Drug: Oral risperidone; QUAR F1/2, Dose 1 - Gluteal; Dose level 1
Experimental: Cohort 1a/2a; 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.	Drug: Oral risperidone; QUAR F1/2, Dose 2 - Gluteal; Dose level 2
Experimental: Cohort 1b//2b; 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.	Drug: Oral risperidone; QUAR F1/2, Dose 3 - Gluteal; Dose level 3
Experimental: Cohort 1c/2c; 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.	Drug: Oral risperidone; QUAR F1/2, Dose 3 - Deltoids; Dose level 3

What is the study measuring?

Primary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Rovi Pharmaceuticals Laboratories

Study record dates

Study Major Dates

• Study Start (Actual): September 26, 2023
• Primary Completion (Estimated): May 1, 2026
• Study Completion (Estimated): May 1, 2026

Study Registration Dates

• First Submitted: February 16, 2024
• First Submitted That Met QC Criteria: February 16, 2024
• First Posted (Actual): February 26, 2024

Study Record Updates

• Last Update Posted (Actual): March 12, 2024
• Last Update Submitted That Met QC Criteria: March 7, 2024
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Schizophrenia Spectrum and Other Psychotic Disorders; Schizophrenia; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Antipsychotic Agents; Tranquilizing Agents; Psychotropic Drugs; Serotonin Agents; Dopamine Agents; Serotonin Antagonists; Dopamine Antagonists; Risperidone
• Other Study ID Numbers: ROV-QUAR-2023-01

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No