AzTrials
AzTrials

Acute SchizophreniaPhase 3PRISMA-3NCT03160521

Study to Evaluate the Efficacy and Safety of Risperidone in Situ Microparticle (ISM)® in Patients With Acute Schizophrenia

A Phase 3 study testing Risperidone ISM 75 mg and Risperidone ISM 100 mg in people with Acute Schizophrenia, run by Rovi Pharmaceuticals Laboratories at 31 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

This is a multicenter, randomized, double-blind, placebo-controlled study designed to evaluate the efficacy and safety of intramuscular (IM) injections of Risperidone ISM® (75 or 100 mg) or placebo, in patients with acute exacerbation of schizophrenia. Read more about this study

Who is it for?
Ages 18 to 65 years
Conditions the study is for
Acute Schizophrenia
What is being tested?
Risperidone ISM 75 mg and Risperidone ISM 100 mg
Type of treatment
Injection or infusion
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
438 participants
Where
31 sitesin 2 countries
Study dates
2 Jun 2017to 17 Dec 2018
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 65 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • To be eligible for enrolment into the study, each patient must meet all of the following criteria at screening:
  • Capable of providing informed consent
  • A signed informed consent form must be provided before any study assessments are performed
  • Patients must be fluent in the language that is spoken by the investigator and the study site staff (including raters) and must be able to read and understand the words in which the informed consent is written
  • Age ≥ 18 and ≤ 65 years
  • Body mass index 18.5 to 40.0 kg/m2 (inclusive)
Show all 23Show fewer
  • Current diagnosis of schizophrenia, according to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) criteria
  • Currently experiencing an acute exacerbation or relapse with onset < 2 months before screening
  • If inpatient at screening, has been hospitalized for < 2 weeks for the current exacerbation
  • ≥ 2 years have elapsed since initial onset of active-phase schizophrenia symptoms
  • Has been able to achieve outpatient status for > 4 months during the past year
  • Has previously had a clinically significant beneficial response (improvement in schizophrenia symptoms), as determined by the investigator, to treatment with an antipsychotic medication other than clozapine
  • Agrees to discontinue prohibited medications as applicable and as clinically indicated according to investigator instructions
  • Dosages of all permitted medications are considered to have been stable (with the exception of medication to be used on an as-needed basis) for ≥ 2 weeks prior to the baseline visit and to remain stable during participation in this study
  • Positive and Negative Syndrome Scale (PANSS) results at the screening and baseline visits meets the following criteria:
  • Total score between 80 and 120, inclusive b. Score of ≥ 4 (moderate or greater) for ≥ 2 of the following Positive Scale items: i. Item 1 (P1: delusions) ii. Item 2 (P2: conceptual disorganization) iii. Item 3 (P3: hallucinatory behavior) iv. Item 6 (P6: suspiciousness/persecution)
  • Clinical Global Impression - Severity (CGI-S) score of ≥ 4 (moderately ill or worse)
  • Resides in a stable living situation and is anticipated to return to that same stable living situation after discharge from the inpatient study unit, in the opinion of the investigator
  • Has an identified reliable informant who is anticipated to remain the same after the patient is discharged from the inpatient study unit, in the opinion of the investigator
  • Meets the following criteria:
  • If a sexually active, is using a medically accepted contraceptive method, and will continue to use such throughout participation in this study (and for ≥ 6 months after the last dose of IM study drug has been administered); acceptable methods include the following: i. Condoms (male or female) with or without a spermicidal agent ii. Diaphragm or cervical cap with spermicide iii. Intrauterine device iv. Hormonal contraceptive b. If not currently sexually active, them meets the following criteria: i. Agrees that if sexually activity resumes while participating in this study, a medically accepted contraception method will be used
  • Willing and able to be confined to an inpatient study unit for up to 2 weeks (or longer if clinically indicated), as applicable and as clinically indicated according to investigator instructions
  • Agrees not to post any personal medical data related to the study or information related to the study on any website or social media site (eg, Facebook, Twitter, and others) during the study duration

Who cannot join

  • An individual who meets any of the following criteria at screening will not be permitted to enroll in the study:
  • History of proven inadequate clinical response to treatment with therapeutic doses (with good compliance) of risperidone or paliperidone
  • History of treatment resistance, defined as failure to respond to 2 discrete adequate trials (≥ 4 weeks with an adequate dose) of 2 different antipsychotic medications; history of clozapine use (exception: use was not because of treatment resistance or refractory psychotic symptoms)
  • Improvement in PANSS total score 20% or greater between the initial screening visit and first injection
  • Known or suspected intolerance of or allergy or hypersensitivity to risperidone, paliperidone, or any of the excipients in the IM formulations of these
  • History of neuroleptic malignant syndrome, clinically significant tardive dyskinesia, or tardive dystonia
Show all 42Show fewer
  • History of any other medical condition that is considered to pose any unjustifiable risk or interfere with study assessments
  • Clinically significant extrapyramidal symptoms at screening or baseline
  • Answer of "yes" on item 4 or on item 5 of the Columbia-Suicide Severity Rating Scale (C-SSRS) (ideation) with the most recent episode occurring within the past 2 months, or answer "yes" to any of the 5 items (behavior) with an episode occurring within the last year
  • Current diagnosis or a history of substance use disorder according to DSM-5 criteria within 6 months prior to the screening visit (with the exception of tobacco, mild cannabis, or mild alcohol use disorder) or a positive drug screen test (with the exception of cannabis) verified by repeat testing
  • Lifetime history of diagnosis of schizoaffective disorder or bipolar disorder
  • Clinically significant comorbid neuropsychiatric disorders including any of the following:
  • Current untreated or unstable major depressive disorder
  • Clinically significant cognitive difficulties including dementia, delirium, or amnesic syndrome, within the past 2 years and would interfere with participation in the study
  • Any other psychiatric condition that would, in the judgment of the investigator, interfere with participation in the study
  • Clinically significant or unstable medical illness/condition/disorder that would be anticipated, in the investigator's opinion, to potentially compromise patient safety or adversely affect the evaluation of efficacy, including (but not necessarily limited to) the following:
  • Clinically significant hypotension or hypertension not stabilized by medical therapy (diastolic blood pressure > 105 mmHg)
  • Unstable thyroid dysfunction in the past 6 months
  • Malignant tumor within the last 5 years
  • Neurologic conditions including the following:
  • History of seizure disorder or condition associated with seizures ii. History of brain tumor, subdural hematoma, or other clinically significant neurological condition within the past 12 months iii. Head trauma with loss of consciousness within 12 months before screening iv. Active acute or chronic central nervous system infection v. Stroke within 6 months before screening e. Cardiac conditions including the following: i. Clinically significant cardiac arrhythmia, cardiomyopathy, or cardiac conduction defect ii. History of myocardial infarction or unstable angina within the last 3 months before screening, or clinically significant abnormality on screening or baseline electrocardiogram (ECG) including but not limited to the following: QT interval corrected for heart rate using Fridericia's formula (QTcF) > 465 msec if male or > 485 msec if female
  • Laboratory abnormality that, in the opinion of the investigator, would compromise the well-being of the patient, or any of the following laboratory abnormalities at screening or baseline:
  • Aspartate aminotransferase or alanine aminotransferase value ≥ 2 times the upper limit of the laboratory normal reference range
  • Hemoglobin A1c > 9%
  • Absolute neutrophil count ≤ 1.5 × 103 μL
  • Platelet count ≤ 75 × 103 μL
  • Creatinine clearance < 60 mL/min
  • Positive test result for human immunodeficiency virus, hepatitis B surface antigen, or antihepatitis C virus antibody
  • Positive pregnancy test result
  • Urine drug screen at screening or baseline shows a positive result for any of the tested substances (potential exceptions: results positive for benzodiazepine may not be exclusionary if the investigator confirms that such medication was medically indicated and consults the medical monitor before enrolling a patient with such a finding; results positive for Tetrahydrocannabinol (THC) may not be exclusionary in certain cases only if exclusion criterion 9 is not met and only if the medical monitor provides approval)
  • Pregnant, lactating, or breastfeeding
  • Inadequate gluteal or deltoid musculature or excessive fat, as determined by the investigator, that would interfere with IM study drug injections
  • Any contraindication for IM injections
  • Receipt of any long-acting antipsychotic medication by IM injection within 60 days before screening
  • Current involuntary hospitalization or incarceration
  • Hospitalized for more than 30 days during the 90 days before screening
  • Participation in another clinical study in which the patient received an experimental or investigational drug or agent within 6 months before screening
  • Participation in a clinical study with Risperidone ISM within 1 year before screening
  • Study site personnel and/or persons employed by the investigator or study site or is an immediate family member of such persons
  • Patients taking any prohibited concomitant medication (see Section 3.2.2.1.1) at the time of randomization visit
  • Clinically significant ocular disease or visual impairment interfering with the planned ophthalmological examinations or that in the investigator's opinion could potentially compromise patients' ocular safety
  • Patients with planned or anticipated need for ocular surgery during the treatment period of the trial

Trial locations and contacts

31 sites in 2 countries.

31 sites in 2 countries

United States20 sites

  • Atlanta Center for Medical Research

    Atlanta, Georgia, 30331

  • Community Clinical Research Inc.

    Austin, Texas, 78754

  • Hassman Research Institute

    Berlin, New Jersey, 08009

  • CIMU Bellflower

    Cerritos, California, 90703

  • Carolina Clinical Triasl Inc

    Charleston, South Carolina, 29407

  • Midwest Clinical Research Center

    Dayton, Ohio, 45417

  • InSite Clinical Research

    DeSoto, Texas, 75115

  • Precise Research Centers MS

    Flowood, Mississippi, 39232

  • CBH Health LLC

    Gaithersburg, Maryland, 20877

  • Collaborative Neuroscience Network, LLC.

    Garden Grove, California, 92845

  • Galiz Research

    Hialeah, Florida, 33016

  • Innovative Clinical Research Inc.

    Hollywood, Florida, 33021

  • Altea Research Institute

    Las Vegas, Nevada, 89102

  • Synergy Research San Diego

    Lemon Grove, California, 91945

  • Apostle Clinical Trials

    Long Beach, California, 90813

  • NRC Research Institute

    Orange, California, 92868

  • CNRI-Los Angeles LLC

    Pico Rivera, California, 90660

  • Pillar Clinical Research LLC

    Richardson, Texas, 75080

  • Woodland Research Northwest

    Rogers, Arkansas, 72758

  • CNRI-San Diego

    San Diego, California, 92112

Other trials in United States

Ukraine11 sites

  • Regional Clinical Hospital n.a I.I. Mechnicov

    Dnipro, 49005

  • Kharkiv Regional Clinical Psychiatric Hospital

    Kharkiv, 61068

  • Public Healthcare Institution "Kharkiv Regional Clinical Psychiatric Hospital No. 3", Center of Urgent Psychiatry

    Kharkiv, 61068

  • Kherson Regional Psychiatric Hospital

    Kherson, 73488

  • Kiev City Psychiatric Hospital No. 2

    Kiev, 02192

  • Kyiv Regional Medical Association "Psykhiatriya" in Kyiv

    Kiev, 04080

  • CI Lviv Regional Clinical Psychiatric Hospital. Department 20

    Lviv, 79021

  • CI Lviv Regional Clinical Psychiatric Hospital. Department 25

    Lviv, 79021

  • Odesa Regional Medical Centre of Mental Health

    Odesa, 65006

  • Maltsev Regional Clinical Psychiatric Ho

    Poltava, 36013

  • N.I. Pyrogov Vinnytsya Natl Medical University

    Vinnytsia, 21005

Other trials in Ukraine

About this study

Official title: Multicenter, Randomized, Double-Blind, Placebo-controlled Study to Evaluate the Efficacy and Safety of Intramuscular Injections of Risperidone ISM® in Patients With Acute Exacerbation of Schizophrenia

This is a multicenter, randomized, double-blind, placebo-controlled study designed to evaluate the efficacy and safety of intramuscular (IM) injections of Risperidone ISM® (75 or 100 mg) or placebo, in patients with acute exacerbation of schizophrenia.

Read the detailed description

The study design includes a screening period, a 12-week treatment period, and a follow-up period. Eligible patients will be randomly assigned, under double-blind conditions, to receive the following study drug treatments in a 1:1:1 ratio during the double-blind treatment period: Risperidone ISM® 75 mg, Risperidone ISM® 100 mg, or placebo. The IM study drug (double-blind active Risperidone ISM® or placebo) will be administered in a deltoid or gluteal muscle for a total of 3 times, once every 4 weeks, during the 12-week treatment period.

If indicated for an individual patient, prohibited medications may be washed out during the screening period. Patients who have never taken Risperidone must have a brief trial of oral Risperidone in order to ensure a lack of any clinically significant hypersensitivity reactions before the first dose of the study drug is administered.

Efficacy will be assessed by describing changes in scores on standard psychiatric assessment tools at each visit. Safety assessments will also be conducted at each visit.

The primary objective of this study is the following:

  • To evaluate the efficacy of Risperidone ISM as compared with that of placebo in the treatment of patients with acute exacerbation of schizophrenia

The secondary objectives of this study are the following:

  • To characterize safety and tolerability of Risperidone ISM as compared with that of placebo in patients with acute exacerbation of schizophrenia
  • To quantify healthcare resource utilization (HRU), health-related quality of life (HRQL), and social functioning in patients treated with Risperidone ISM versus placebo for an acute exacerbation of schizophrenia
  • To explore pharmacokinetic characteristics of Risperidone ISM and associations with efficacy

Patients who complete planned double-blind study drug treatments and study evaluations may be eligible to participate in an optional long-term extension segment of the study in which treatment with open-label Risperidone ISM 75 or 100 mg (randomly assigned) would begin immediately; for patients who do not participate in the extension segment, a safety follow-up phone contact will occur after the end-of-treatment visit.

In addition to patients continuing from the double-blind segment of the study (rollover patients), patients not previously enrolled in the study (de novo patients) may be eligible to enter the long-term extension segment of the study. These patients will be evaluated for eligibility at a screening visit and, if eligible, will be allocated to receive either 75 or 100 mg Risperidone ISM every 4 weeks for approximately 12 months.

Being tested
Risperidone ISM 75 mg, Risperidone ISM 100 mg, Placebo of Risperidone ISM

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Risperidone ISM 75 mgDrug

    Also called Risperidone ISM

    Monthly (once every 4 weeks) IM injection in the gluteal or deltoid muscle.

  • Risperidone ISM 100 mgDrug

    Also called Risperidone ISM

    Monthly (once every 4 weeks) IM injection in the gluteal or deltoid muscle.

  • Placebo of Risperidone ISMDrug

    Also called PLACEBO

    Monthly (once every 4 weeks) IM injection in the gluteal or deltoid muscle.

Study groups in NCT03160521
Study groupRoleWhat they receive
Risperidone ISM 75 mgExperimentalPatients assigned to this arm will received 75 mg of Risperidone ISM during double-blind treatment period.
Receives: Drug: Risperidone ISM 75 mg
Risperidone ISM 100 mgExperimentalPatients assigned to this arm will received 100 mg of Risperidone ISM during double-blind treatment period.
Receives: Drug: Risperidone ISM 100 mg
PlaceboPlacebo comparatorPatients assigned to this arm will received placebo of Risperidone ISM during double-blind treatment period.
Receives: Drug: Placebo of Risperidone ISM

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. PANSS Total Score Mean Change From Baseline to Endpoint

    The Positive and Negative Syndrome Scale (PANSS) is a 30-item clinician-rated instrument for assessing the symptoms of schizophrenia.The 30 symptoms are rated on a 7-point scale that ranges from 1 (absent) to 7 (extreme psychopathology). The PANSS total score is the sum of all 30 PANSS items and ranges from 30 to 210, with 30 indicating absence of symptoms of schizophrenia and 210 indicating extreme ratings of all 30 symptoms. Negative change from baseline scores indicate improvements in symptoms whereas higher scores mean a worse outcome.

    Endpoint is defined as study day 85 or the last post-baseline assessment if early discontinuation.

    Measured: Day 1 (Baseline) and Day 85 (or the last post-baseline assessment)

Secondary outcomes (7)

  1. CGI-S Total Score Mean Change From Baseline to Endpoint

    The Clinician Global Impression - Severity (CGI-S) score is a 7-point clinician-rated scale for assessing the global severity of the illness. A rating of 1 is equivalent to "Normal, not at all ill" and a rating of 7 is equivalent to "Among the most extremely ill participants". Negative change from baseline scores indicate improvement in the severity of illness whereas higher scores mean a worse outcome.

    Endpoint is defined as study day 85 or the last post-baseline assessment if early discontinuation.

    Measured: Day 1 (Baseline) and Day 85 (or the last post-baseline assessment)

  2. CGI-I Score Mean at Endpoint

    The Clinical Global Impression - Improvement (CGI-I) Score consists of a single 7-point rating score total improvement, regardless of whether or not the change it is due entirely to drug treatment.

    Scores are: 1, Very much improved; 2, Much improved; 3, Minimally improved; 4, No change; 5, Minimally worse; 6, Much worse; or 7, Very much worse.

    Endpoint is defined as study day 85 or the last post-baseline double-blind assessment if early discontinuation.

    Measured: Day 1 (Baseline) and Day 85 (or the last post-baseline assessment)

  3. Overall Response Rate at Endpoint

    Overall response was defined as either PANSS total score ≥ 30% decrease from baseline, or CGI-I score of 2 (much improved) or 1 (very much improved).

    Endpoint is defined as study day 85 or the last post-baseline assessment if early discontinuation.

    Measured: Day 85 or the last post-baseline assessment

  4. PANSS Response Rate at Endpoint

    The definition of Positive and Negative Syndrome Scale (PANSS) response was a decrease from baseline in PANSS total score of ≥ 30% (improvement of symptoms).

    Endpoint is defined as study day 85 or the last post-baseline double-blind assessment if early discontinuation.

    Measured: Day 85 or the last post-baseline assessment

  5. PANSS Positive Subscale Mean Change From Baseline to Endpoint

    The PANSS consisted of three subscales that contained a total of 30 symptom constructs. For each symptom construct, severity is rated on a 7-point scale, with a score of 1 indicated the absence of symptoms and a score of 7 indicated extremely severe symptoms. In positive subscale, the 7 positive symptom constructs were: delusions, conceptual disorganization, hallucinatory behavior, excitement, grandiosity, suspiciousness/persecution, and hostility.

    PANSS Positive Subscale Score ranges from 7 (absence of symptoms) to 49 (extremely severe symptoms).

    Endpoint is defined as study day 85 or the last post-baseline assessment if early discontinuation.

    Measured: Day 1 (Baseline) and Day 85 (or the last post-baseline assessment)

  6. PANSS Negative Subscale Mean Change From Baseline to Endpoint

    The PANSS consisted of three subscales: a total of 30 symptom constructs. For each symptom construct, severity was rated on a 7-point scale, with a score of 1 indicated- absence of symptoms and a score of 7 indicated- extremely severe symptoms. The PANSS negative subscale score was the sum of the rating scores for the 7 negative scale items from the PANSS panel. The 7 negative symptom constructs were: blunted affect, emotional withdrawal, poor rapport, passive apathetic withdrawal, difficulty in abstract thinking, lack of spontaneity and flow of conversation and stereotyped thinking. PANSS Negative Subscale Score ranges from 7 (absence of symptoms) to 49 (extremely severe symptoms).

    Endpoint is defined as study day 85 or the last post-baseline assessment if early discontinuation.

    Measured: Day 1 (Baseline) and Day 85 (or the last post-baseline assessment)

  7. PANSS General Psychopathology Subscale Mean Change From Baseline to Endpoint

    The PANSS consisted of three subscales that contained a total of 30 symptom constructs. For each symptom construct, severity is rated on a 7-point scale, with a score of 1 indicated the absence of symptoms and a score of 7 indicated extremely severe symptoms. The general psychopathology scale consists of 16 items which measure somatic concern, anxiety, guilt feelings, tension, mannerisms and posturing, depression, motor retardation, uncooperativeness, unusual thought content, disorientation, poor attention, lack of judgment and insight, disturbance of volition, poor impulse control, preoccupation and active social avoidance. PANSS General Psychopathology Subscale Score ranges from 16 (absence of symptoms) to 112 (extremely severe symptoms).

    Endpoint is defined as study day 85 or the last post-baseline assessment if early discontinuation.

    Measured: Day 1 (Baseline) and Day 85 (or the last post-baseline assessment)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted19 May 2017
  2. Study start2 Jun 2017
  3. Primary completion17 Dec 2018
  4. Study completion17 Dec 2018

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Triple blind
Who is masked
Participant, Care provider, Investigator
Enrolment
438 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03160521
Sponsor's protocol ID
ROV-RISP-2016-01
Acronym
PRISMA-3
Status last verified
Jan 2022
First submitted
12 May 2017
Last updated
22 Feb 2022
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • Correll CU, Litman RE, Filts Y, Llaudo J, Naber D, Torres F, Martinez J. Efficacy and safety of once-monthly Risperidone ISM(R) in schizophrenic patients with an acute exacerbation. NPJ Schizophr. 2020 Nov 25;6(1):37. doi: 10.1038/s41537-020-00127-y.

    PubMed 33239746

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Risperidone ISM 75 mg and Risperidone ISM 100 mg in people with Acute Schizophrenia, run by Rovi Pharmaceuticals Laboratories at 31 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 23 inclusion and 42 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 22 Feb 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 31 sites in United States, Ukraine. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 4 Feb 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

PANSS Total Score Mean Change From Baseline to Endpoint (time frame: Day 1 (Baseline) and Day 85 (or the last post-baseline assessment)). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03160521, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Feb 2022.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in
PRISMA-3 Clinical Trial NCT03160521 | AzTrials