Clinical trial NCT06276361: Pharmacokinetics, Safety and Tolerability of Different Formulations and Dose Strengths of Quarterly Risperidone (QUAR) in Patients With Schizophrenia
Official title: 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)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Schizophrenia
Lead sponsor: Rovi Pharmaceuticals Laboratories
Sponsor class: INDUSTRY
First posted: 2024-02-26
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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-).

Eligibility criteria: 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.

Primary outcomes:
measure: λz
timeFrame: Following Oral and QUAR administration until day 17 or 196 respectively
measure: t1/2
timeFrame: Following Oral and QUAR administration until day 17 or 196 respectively
measure: Tmax
timeFrame: Following Oral and QUAR administration until day 17 or 196 respectively
measure: Cmax
timeFrame: Following Oral and QUAR administration until day 17 or 196 respectively
measure: Cmin
timeFrame: Following Oral and QUAR administration until day 17 or 196 respectively
measure: Clast
timeFrame: Following Oral and QUAR administration until day 17 or 196 respectively
measure: AUC0-t
timeFrame: Following Oral and QUAR administration until day 17 or 196 respectively
measure: AUCinf
timeFrame: Following QUAR administration until day 196
measure: AUCextrap
timeFrame: Following QUAR administration until day 196
measure: Vd/F
timeFrame: Following Oral and QUAR administration until day 17 or 196 respectively
measure: Cl/F
timeFrame: Following Oral and QUAR administration until day 17 or 196 respectively
Secondary outcomes:
Other outcomes:
Locations:
city: Amman
country: Jordan
facility: Investigational Site
Study officials:
References: