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CompletedNCT02164981Updated Oct 2, 2018Results posted

A Proof of Concept Study of Intravenous Sodium Nitroprusside in Adults With Symptomatic Schizophrenia

A Phase 2 interventional study of sodium nitroprusside and Placebo in Schizophrenia, sponsored by Massachusetts General Hospital. Completed at 4 sites in United States. Open to participants aged 18 Years to 65 Years. Per ClinicalTrials.gov, last updated 2018-10-02.

Sponsored by Massachusetts General Hospital · Phase 2, Interventional, and Treatment

Phase
Phase 2
Study type
Interventional
Enrollment
60
Allocation
Randomized
Ages
18 Years to 65 Years
Sex
All
01

Study summary

The primary objective of this study is to investigate whether a single infusion of intravenous sodium nitroprusside (0.5 μg/kg/min for 4 hours) is superior to placebo (5% dextrose solution) at in treating positive and negative symptoms of schizophrenia

Read the detailed description

This is a phase II proof of concept (POC), multi-center, prospective, randomized, placebo-controlled, Sequential Parallel Comparison Design (SPCD) study, in which a total of 60 subjects with schizophrenia will be enrolled.

The study will be conducted in two stages. The study treatment will be administered in a double-blind fashion for all subjects throughout both stages of the study. A total of 60 subjects with schizophrenia will be randomized in a 1:1:1 ratio to drug-drug sequence [n=20; i.v. sodium nitroprusside (0.5 μg/kg/min for 4 hours) at week 0 and week 2], placebo-drug sequence [n=20; i.v. placebo at week 0 and i.v. sodium nitroprusside (0.5 μg/kg/min for 4 hours) at week 2], and placebo-placebo sequence [n=20; i.v. placebo at week 0 and again at week 2]. The 4-week double-blind phase of treatment will be divided into two phases: Phase 1, from week 0 to week 2, and Phase 2 from week 2 to week 4. At the end of Phase 1 (week 2), the randomized subjects will be assessed and categorized into responders and non-responders, based on 20% or more reduction from baseline in their PANSS total score as per the evaluations at Randomization Visit (week 0). The data from the patients deemed placebo non-responders in phase 1 who go on to either stay on placebo or to receive treatment with sodium nitroprusside will be pooled with the data from Phase 1 from all subjects, according to SPCD.

02

Conditions studied

  • Schizophrenia

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03

In context

Schizophrenia

3,471 studies on the registry are indexed under Schizophrenia; 472 are open to participants now.

This study's enrollment of 60 is below the median of 70 across 2,872 interventional studies indexed under Schizophrenia.

Browse Schizophrenia studies →

Lead sponsor

Massachusetts General Hospital is the lead sponsor of 2,536 studies on the registry; 446 are open to participants now.

Of its 214 completed or terminated interventional studies of FDA-regulated products, 161 (75%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years to 65 Years
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

Each subject must meet all of the following criteria to be eligible for this study:

  1. Males or Females aged 18-65 years inclusive.
  2. Primary diagnosis of Schizophrenia established by a structured psychiatric evaluation (SCID) based on Diagnostic and Statistical Manual of Mental Disorders Forth Edition (DSM-IV-TR) criteria.
  3. Written informed consent in compliance with 21 CFR part 50 and in accordance with the International Conference on Harmonization (ICH) Good Clinical Practice (GCP) Guidelines.
  4. A Positive and Negative Syndrome Scale (PANSS) (Kay et al., 1994) total score ≥ 70 with a score of > 4 on two or more of the following PANSS items: delusions, conceptual disorganization, hallucinatory behavior, suspiciousness, and unusual thought content.
  5. A score of ≥4 on the Clinical Global Impression-Severity (CGI-S) (Guy, 1976).
  6. Confirmation of both diagnosis and severity of psychosis symptoms by an independent MGH SAFER interview.
  7. Must have ongoing antipsychotic treatment for at least 8 weeks, with a stable dose for at least 4 weeks. Subjects who have failed to achieve clinically-recognized symptom reduction to at least 1 marketed antipsychotic agent, given at a Physician Desk Reference (PDR)-defined therapeutic dose for ≥ 8 weeks during the past 12 months, as assessed by the MGH FAST, will be eligible
  8. Understands and is able, willing, and (in the opinion of the investigator) likely to fully comply with the study procedures and restrictions.

Exclusion criteria

Exclusion Criteria

Subjects who meet any of the following criteria will be excluded from the study:

  1. Subjects with a history of renal insufficiency, congestive heart failure, cardiac arrhythmias or history of myocardial infarction.
  2. Subjects with a history of symptomatic orthostatic hypotension defined as sitting to standing systolic blood pressure \< 90mmHg or diastolic blood pressure \< 60mm Hg with any of the following symptoms: lightheaded or dizzy upon standing, blurry vision, weakness, fainting (syncope), confusion, or nausea.
  3. Subjects with any clinically significant abnormalities as determined by medical history, physical exam, clinical and lab evaluation suggestive of an underlying disease state that may, in the opinion of the investigator, confound the results of study, increase risk to the subject, or lead to difficulty complying with the protocol.
  4. Subjects on chlorpromazine, PDE-5 inhibitors, nitrites and any medication with CNS effects with the exception of antipsychotic drugs (other than chlorpromazine) anticholinergics, b-adrenergic antagonists, amantadine, biperiden, diphenhydramine, lorazepam, zolpidem, and temazepam.
  5. Medications which in the opinion of the PI, and in conjunction with the medical monitor, may be expected to significantly interfere with the metabolism or excretion of sodium nitroprusside, and/or may be associated with a significant drug interaction with sodium nitroprusside that may pose a significant risk to subjects' health and/or confound the study data.
  6. Pregnant or breast-feeding patients. Women of childbearing potential must have a negative pregnancy test performed at screening visit prior to randomization and prior to baseline at visits 3 and 6. Women enrolled in this trial must use adequate birth control.
  7. Subjects with a current (within the last 3 months) DSM-IV-TR diagnosis of alcohol or substance use disorder or dependence (excluding nicotine) as established by the clinical assessment (SCID) at the screening visit will be excluded.
  8. Has tested positive for any of the following: cannabis, opioids, cocaine, amphetamines, barbiturates methadone, methamphetamine and phencyclidine at the screening or baseline visits. If positive, the urine drug toxicology screen may be repeated once based on investigator judgment, but due to safety concerns, the result must be negative for the subject to continue in the study.
  9. Subjects at imminent risk of suicide or injury to self or others, as per the opinion of the investigator, or history of significant suicide attempt within the last 6 months as per C-SSRS.
  10. Subjects that have taken an investigational drug or taken part in a clinical trial within 30 days prior to screening.
  11. Any other reason that, in the opinion of the investigator, would compromise patient safety or integrity of the study
05

Study design

Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Crossover assignment
Masking
Triple (Participant, Care provider, Investigator)
Enrollment
60 participants (actual)

Study arms

  • Active comparator
    Drug - Drug

    Phase 1 - intravenous sodium nitroprusside Phase 2 - intravenous sodium nitroprusside

    Drug: sodium nitroprusside

  • Other
    Placebo - Drug

    Phase 1 - intravenous dextrose Phase 2 - intravenous sodium nitroprusside

    Drug: sodium nitroprusside

  • Placebo comparator
    Placebo - Placebo

    Phase 1 - intravenous dextrose Phase 2 - intravenous dextrose

    Other: Placebo

Interventions

  • Drugsodium nitroprusside

    intravenous

    Also known as: Nitropress

  • OtherPlacebo

    Placebo

    Also known as: 5% dextrose

06

What researchers measure

Primary outcomes

  1. Change in Positive and Negative Syndrome Scale (PANSS) - Total Score - Study Phases 1 and 2

    The Positive and Negative Syndrome Scale (PANSS) will be used to measure symptom severity in this trial. PANSS is a 30-item questionnaire used to evaluate schizophrenia symptoms, based on the clinical interview as well as reports of family members or primary care hospital workers. PANSS consists of Positive scale (7 items), Negative scale (7 items), and General Psychopathological scale (16 items) sections. Each item (symptom) will be scored on a 7-point scale with higher scores representing increasing levels of psychopathology: 1) Absent, 2) Minimal, 3) Mild, 4) Moderate, 5) Moderate severe, 6) Severe, and 7) Extreme. Total score minimum = 30, maximum = 210

    Time frame: For Phase 1, timeframe is Day 0 and Day 14; Phase 2 timeframe is Day 14 and Day 28

Secondary outcomes

  1. PANSS - Positive Subscale - Phases 1 and 2

    The Positive and Negative Syndrome Scale (PANSS) will be used to measure symptom severity in this trial. PANSS is a 30-item questionnaire used to evaluate schizophrenia symptoms, based on the clinical interview as well as reports of family members or primary care hospital workers. PANSS consists of Positive scale (7 items), Negative scale (7 items), and General Psychopathological scale (16 items) sections. Each item (symptom) will be scored on a 7-point scale with higher scores representing increasing levels of psychopathology: 1) Absent, 2) Minimal, 3) Mild, 4) Moderate, 5) Moderate severe, 6) Severe, and 7) Extreme. Positive scale: 7 Items, (minimum score = 7, maximum score = 49)

    Time frame: Phase 1 timeframe is Baseline and Day 14; Phase 2 timeframe is Day 14 and Day 28

  2. PANSS - Negative Subscale - Phases 1 and 2

    The Positive and Negative Syndrome Scale (PANSS) will be used to measure symptom severity in this trial. PANSS is a 30-item questionnaire used to evaluate schizophrenia symptoms, based on the clinical interview as well as reports of family members or primary care hospital workers. PANSS consists of Positive scale (7 items), Negative scale (7 items), and General Psychopathological scale (16 items) sections. Each item (symptom) will be scored on a 7-point scale with higher scores representing increasing levels of psychopathology: 1) Absent, 2) Minimal, 3) Mild, 4) Moderate, 5) Moderate severe, 6) Severe, and 7) Extreme. Negative scale: 7 Items, (minimum score = 7, maximum score = 49)

    Time frame: Phase 1 timeframe is Day 0 and Day 14; Phase 2 timeframe is Day 14 and Day 28

  3. PANSS - General Psychopathology Subscale - Phases 1 and 2

    The Positive and Negative Syndrome Scale (PANSS) will be used to measure symptom severity in this trial. PANSS is a 30-item questionnaire used to evaluate schizophrenia symptoms, based on the clinical interview as well as reports of family members or primary care hospital workers. PANSS consists of Positive scale (7 items), Negative scale (7 items), and General Psychopathological scale (16 items) sections. Each item (symptom) will be scored on a 7-point scale with higher scores representing increasing levels of psychopathology: 1) Absent, 2) Minimal, 3) Mild, 4) Moderate, 5) Moderate severe, 6) Severe, and 7) Extreme. General Psychopathology Subscale: 16 Items, (minimum score = 16, maximum score = 112)

    Time frame: Phase 1 timeframe is Baseline and Day 14; Phase 2 timeframe is Day 14 and Day 28

  4. Average Percent Change From Baseline in the PANSS Total Score After 2 Weeks of Treatment Using SPCD

    The Positive and Negative Syndrome Scale (PANSS) will be used to measure symptom severity in this trial. PANSS is a 30-item questionnaire used to evaluate schizophrenia symptoms, based on the clinical interview as well as reports of family members or primary care hospital workers. PANSS consists of Positive scale (7 items), Negative scale (7 items), and General Psychopathological scale (16 items) sections. Each item (symptom) will be scored on a 7-point scale with higher scores representing increasing levels of psychopathology: 1) Absent, 2) Minimal, 3) Mild, 4) Moderate, 5) Moderate severe, 6) Severe, and 7) Extreme. Total score minimum = 30, maximum = 210.

    Time frame: For Phase 1, timeframe is Baseline and Day 14; Phase 2 timeframe is Day 14 and Day 28

  5. Percentage of Subjects With 20% or More Reduction From Baseline in PANSS Total Score After 2 Weeks of Treatment Using SPCD

    The Positive and Negative Syndrome Scale (PANSS) will be used to measure symptom severity in this trial. PANSS is a 30-item questionnaire used to evaluate schizophrenia symptoms, based on the clinical interview as well as reports of family members or primary care hospital workers. PANSS consists of Positive scale (7 items), Negative scale (7 items), and General Psychopathological scale (16 items) sections. Each item (symptom) will be scored on a 7-point scale with higher scores representing increasing levels of psychopathology: 1) Absent, 2) Minimal, 3) Mild, 4) Moderate, 5) Moderate severe, 6) Severe, and 7) Extreme. Total score minimum = 30, maximum = 210.

    Time frame: For Phase 1, timeframe is Baseline and Day 14; Phase 2 timeframe is Day 14 and Day 28

  6. Average Percent Change From Baseline in the PANSS Positive Subscale Score After 2 Weeks of Treatment Using SPCD

    The Positive and Negative Syndrome Scale (PANSS) will be used to measure symptom severity in this trial. PANSS is a 30-item questionnaire used to evaluate schizophrenia symptoms, based on the clinical interview as well as reports of family members or primary care hospital workers. PANSS consists of Positive scale (7 items), Negative scale (7 items), and General Psychopathological scale (16 items) sections. Each item (symptom) will be scored on a 7-point scale with higher scores representing increasing levels of psychopathology: 1) Absent, 2) Minimal, 3) Mild, 4) Moderate, 5) Moderate severe, 6) Severe, and 7) Extreme. Positive subscore scale: 7 items (minimum score = 7; maximum score = 49)

    Time frame: For Phase 1, timeframe is Baseline and Day 14; Phase 2 timeframe is Day 14 and Day 28

  7. Average Percent Change From Baseline in the PANSS Negative Subscale Score After 2 Weeks of Treatment Using SPCD

    The Positive and Negative Syndrome Scale (PANSS) will be used to measure symptom severity in this trial. PANSS is a 30-item questionnaire used to evaluate schizophrenia symptoms, based on the clinical interview as well as reports of family members or primary care hospital workers. PANSS consists of Positive scale (7 items), Negative scale (7 items), and General Psychopathological scale (16 items) sections. Each item (symptom) will be scored on a 7-point scale with higher scores representing increasing levels of psychopathology: 1) Absent, 2) Minimal, 3) Mild, 4) Moderate, 5) Moderate severe, 6) Severe, and 7) Extreme. Negative subscore scale: 7 items (minimum score = 7; maximum score = 49)

    Time frame: For Phase 1, timeframe is Baseline and Day 14; Phase 2 timeframe is Day 14 and Day 28

  8. Average Percent Change From Baseline in the PANSS General Psychopathology Subscale Score After 2 Weeks of Treatment Using SPCD

    The Positive and Negative Syndrome Scale (PANSS) will be used to measure symptom severity in this trial. PANSS is a 30-item questionnaire used to evaluate schizophrenia symptoms, based on the clinical interview as well as reports of family members or primary care hospital workers. PANSS consists of Positive scale (7 items), Negative scale (7 items), and General Psychopathological scale (16 items) sections. Each item (symptom) will be scored on a 7-point scale with higher scores representing increasing levels of psychopathology: 1) Absent, 2) Minimal, 3) Mild, 4) Moderate, 5) Moderate severe, 6) Severe, and 7) Extreme. General Psychopathology subscore scale: 16 items (minimum score = 16; maximum score = 112)

    Time frame: For Phase 1, timeframe is Baseline and Day 14; Phase 2 timeframe is Day 14 and Day 28

Other outcomes

  1. Change in the Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Consensus Cognitive Battery (MCCB) - Phases 1 and 2

    MATRICS: The Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Consensus Cognitive Battery (MCCB). The MATRICS Consensus Cognitive Battery is the standard tool for assessing cognitive change in trials of cognitive-enhancing agents in schizophrenia. The MCCB domains include: Speed of Processing; Attention/Vigilance; Working Memory; Verbal Learning; Visual Learning; Reasoning \& Problem-Solving; and Social Cognition and the battery takes about 80 minutes to complete. The MCCB composite score represents a global measure of cognition. MCCB composite T scores are between 40 and 60 (normal range) and \< 40 (below normal range).

    Time frame: Phase 1 timeframe is Baseline and Day 14; Phase 2 timeframe is Day 14 and Day 28

  2. Average AIMS Total Scores (Items 1-7) by Group and Timepoint

    Abnormal Involuntary Movement Scale (AIMS): The AIMS Total Dyskinesia Score was calculated by averaging the first 7 items of the AIMS. The 7 items included in the AIMS Dyskinesia Score are rated on a scale from 0 (no dyskinesia) to 4 (severe dyskinesia). Items 1 through 7 include facial and oral movements (Items 1-4), extremity movements (Items 5-6), and trunk movements (Item 7). The AIMS dyskinesia total score ranges from 0 to 4; a higher score reflects increased severity.

    Time frame: Baseline 1 (Day -1), 7 Hours Post-Infusion 1, Baseline 2 (Day 13), 7 Hours Post-Infusion 2, Final Follow-Up, including early termination visits

  3. Percent of Participants Rated as ≥ "Mild" or as "Yes" on AIMS Items 8-12

    Abnormal Involuntary Movement Scale (AIMS): The AIMS is a 12-item anchored score that is clinician administered and scored. Items are scored on a 0 (none) to 4 (severe) basis; items 8-10 deal with global severity; items 11-12 are yes-no questions concerning problems with teeth and/or dentures.

    Time frame: Baseline (Day -1), Follow-Up = reported at any assessment thereafter, including 7 hours after Infusions #1 and #2, Baseline 2 (Day 13) and final follow-up, including early termination visits.

  4. Change in The University of California San Diego (UCSD) Performance-based Skills Assessment Brief (UPSA-B) - Phases 1 and 2

    The University of California San Diego (UCSD) Performance-based Skills Assessment Brief (UPSA-B) consists of two of the five original UPSA domains, finances and communication. Each subscale contributes 50 points; total scores range from 0 to 100 points with higher scores reflecting better performance.

    Time frame: Phase 1 timeframe is Baseline and Day 14; Phase 2 timeframe is Day 14 and Day 28

  5. Number of Participants Reporting Suicidal Ideation/Behavior on the Columbia Suicide Severity Rating Scale (C-SSRS)

    The Columbia Suicide Severity Rating Scale (C-SSRS): The C-SSRS is a low-burden measure of the spectrum of suicidal ideation and behavior that was developed in the National Institute of Mental Health Treatment of Adolescent Suicide Attempters Study to assess severity and track suicidal events through any treatment. It is a clinical interview providing a summary of both ideation and behavior that can be administered during any evaluation or risk assessment to identify the level and type of suicidality present. The C-SSRS can also be used during treatment to monitor for clinical worsening or improvement. It contains 5 rating scale questions (yes/no) for suicidal ideation increasing severity and 5 rating scale questions (yes/no) for suicidal behavior of increasing severity. The time frame is for both lifetime and the past six months for the Baseline/Screening scale and since the last visit for the Since Last Visit scale.

    Time frame: Screening Visit, Days 3 (Baseline 1), Days 7, 13 (Baseline 2), 21 and 28

  6. Systolic Blood Pressure Per Infusion Phase by Group

    Infusion 1 (Day 0) - Systolic Blood Pressure at all time points by group "Phase" in this analysis refers to the infusion stage as defined in the protocol.

    Time frame: Day 0 - Phase 1 - Baseline = min000s1 and @5 min; Phase 2 - Baseline = min000 then every 10 minutes for 4 hours; Post Infusion - Baseline = min000, then every 10 minutes for 2 hours

  7. Diastolic Blood Pressure Per Infusion Phase by Group

    Infusion 1 (Day 0) - Diastolic Blood Pressure at all time points by group "Phase" in this analysis refers to the infusion stage as defined in the protocol.

    Time frame: Day 0 - Phase 1 - Baseline = min000s1 and @5 min; Phase 2 - Baseline = min000 then every 10 minutes for 4 hours; Post Infusion - Baseline = min000, then every 10 minutes for 2 hours

  8. Systolic Blood Pressure Per Infusion Phase by Group

    Infusion 2 (Day 14) - Systolic Blood Pressure at all time points by group "Phase" in this analysis refers to the infusion stage as defined in the protocol.

    Time frame: Day 14 - Phase 1 - Baseline = min000s1 and @5 min; Phase 2 - Baseline = min000 then every 10 minutes for 4 hours; Post Infusion - Baseline = min000, then every 10 minutes for 2 hours

  9. Phase 2 - Diastolic Blood Pressure Per Infusion Phase by Group

    Infusion 2 (Day 14) - Diastolic Blood Pressure at all time points by group

    Time frame: Day 14 - Phase 1 - Baseline = min000s1 and @5 min; Phase 2 - Baseline = min000 then every 10 minutes for 4 hours; Post Infusion - Baseline = min000, then every 10 minutes for 2 hours

  10. Heart Rate Per Infusion Phase by Group

    Infusion 1 (Day 0) - Heart rate at all time points by group "Phase" in this analysis refers to the infusion stage as defined in the protocol.

    Time frame: Day 0 - Phase 1 - Baseline = min000s1 and @5 min; Phase 2 - Baseline = min000 then every 10 minutes for 4 hours; Post Infusion - Baseline = min000, then every 10 minutes for 2 hours

  11. Heart Rate Per Infusion Phase by Group

    Infusion 2 (Day 14) - Heart rate at all time points by group "Phase" in this analysis refers to the infusion stage as defined in the protocol.

    Time frame: Day 14 - Phase 1 - Baseline = min000s1 and @5 min; Phase 2 - Baseline = min000 then every 10 minutes for 4 hours; Post Infusion - Baseline = min000, then every 10 minutes for 2 hours

  12. ECG Measures at All Time Points by Group

    Infusion 1 (Day 0) - ECG measures at all time points by group

    Time frame: Day 0 - Baseline (pre-infusion), During Infusion (@30 min), Post-Infusion (@60min)

  13. ECG Measures at All Time Points by Group

    Infusion 2 (Day 14) - ECG measures at all time points by group

    Time frame: Day 14 - Baseline (pre-infusion), During Infusion (@30 min), Post-Infusion (@60min)

  14. Incidence of Treatment-Emergent Adverse Events (TEAEs)

    Incidence of Treatment-Emergent Adverse Events (TEAE) by Treatment Group. A treatment emergent adverse event (TEAE) is an AE that either began following initiation of study treatment or was present prior to the initiation of the treatment, but increased in frequency or severity following initiation treatment, regardless of causality.

    Time frame: The period of observation for collection of treatment-emergent adverse events extends from Day 0 treatment through the final visit at Day 28.

  15. Number of Subject Withdrawals Due to Treatment-Emergent Adverse Events (TEAEs)

    Incidence of Treatment-Emergent Adverse Events (TEAE) by Treatment Group. A treatment emergent adverse event (TEAE) is an AE that either began following initiation of study treatment or was present prior to the initiation of the treatment, but increased in frequency or severity following initiation treatment, regardless of causality.

    Time frame: The period of observation extends from Day 0 treatment through the final visit at Day 28

  16. Systematic Assessment for Treatment Emergent Effects-Systematic Inquiry (SAFTEE-SI) - Percent of Participants Reporting Experiencing Symptoms at "Moderate" or "Severe" Level for the 10 Most Frequently Reported Symptoms Post Randomization

    The Systematic Assessment for Treatment Emergent Effects-Systematic Inquiry (SAFTEE-SI): This is a self-rated 77-item questionnaire organized into 13 body areas assessing possible adverse events during the course of the trial.

    Time frame: Baseline (Day - 1), Follow-Up = reported at any assessment thereafter, including 7 hours after Infusions #1 and #2, Baseline 2 (Day 13) and final follow-up, including early termination visits.

07

Results

Posted Oct 2, 2018

Participant flow

Started
Participant flow — Started
MilestoneDrug - DrugPlacebo - DrugPlacebo - Placebo
Started231918
Completed181618
Not completed530
Withdrew: Withdrawal by subject210
Withdrew: Protocol violation200
Withdrew: Adverse event120
Phase 1 (Day 0 - Day 14)
Participant flow — Phase 1 (Day 0 - Day 14)
MilestoneDrug - DrugPlacebo - DrugPlacebo - Placebo
Started181618
Completed181418
Not completed020
Withdrew: Adverse event020
Phase 2 (Day 14 - Day 28)
Participant flow — Phase 2 (Day 14 - Day 28)
MilestoneDrug - DrugPlacebo - DrugPlacebo - Placebo
Started181418
Completed161218
Not completed220
Withdrew: Adverse event210
Withdrew: Protocol violation010

Outcome measures

PrimaryChange in Positive and Negative Syndrome Scale (PANSS) - Total Score - Study Phases 1 and 2

The Positive and Negative Syndrome Scale (PANSS) will be used to measure symptom severity in this trial. PANSS is a 30-item questionnaire used to evaluate schizophrenia symptoms, based on the clinical interview as well as reports of family members or primary care hospital workers. PANSS consists of Positive scale (7 items), Negative scale (7 items), and General Psychopathological scale (16 items) sections. Each item (symptom) will be scored on a 7-point scale with higher scores representing increasing levels of psychopathology: 1) Absent, 2) Minimal, 3) Mild, 4) Moderate, 5) Moderate severe, 6) Severe, and 7) Extreme. Total score minimum = 30, maximum = 210

Time frame:
For Phase 1, timeframe is Day 0 and Day 14; Phase 2 timeframe is Day 14 and Day 28
Reported as:
Mean · units on a scale
Change in Positive and Negative Syndrome Scale (PANSS) - Total Score - Study Phases 1 and 2
units on a scaleDrugPlacebo
Phase 1 - Total Score - Baseline83.6 ± 10.079.8 ± 8.9
Phase 1 - Total Score - Day 1477.6 ± 12.276.7 ± 11.0
Phase 1 - Total Score - Change-6.0 ± 11.3-2.5 ± 7.1
Phase 2 - Total Score - Day 1474.0 ± 12.078.8 ± 10.1
Phase 2 - Total Score - Day 2871.8 ± 10.674.7 ± 9.0
Phase 2 - Total Score - Change-1.8 ± 8.2-4.2 ± 6.4
Statistical analysis
  • Drug vs Placebo · ANCOVA · p = 0.57 (No adjustment for multiple comparisons, as there was only one primary outcome variable.) · Mean difference (final values): -1.04
  • Drug vs Placebo · ANCOVA · p = 0.54 (No adjustment for multiple comparisons, as there was only one primary outcome variable.) · Mean difference (final values): -1.09
SecondaryPANSS - Positive Subscale - Phases 1 and 2

The Positive and Negative Syndrome Scale (PANSS) will be used to measure symptom severity in this trial. PANSS is a 30-item questionnaire used to evaluate schizophrenia symptoms, based on the clinical interview as well as reports of family members or primary care hospital workers. PANSS consists of Positive scale (7 items), Negative scale (7 items), and General Psychopathological scale (16 items) sections. Each item (symptom) will be scored on a 7-point scale with higher scores representing increasing levels of psychopathology: 1) Absent, 2) Minimal, 3) Mild, 4) Moderate, 5) Moderate severe, 6) Severe, and 7) Extreme. Positive scale: 7 Items, (minimum score = 7, maximum score = 49)

Time frame:
Phase 1 timeframe is Baseline and Day 14; Phase 2 timeframe is Day 14 and Day 28
Reported as:
Mean · units on a scale
PANSS - Positive Subscale - Phases 1 and 2
units on a scaleDrugPlacebo
Phase 1 - Positive Score - Baseline24.5 ± 3.522.3 ± 3.1
Phase 1 - Positive Score - Day 1423.1 ± 4.621.3 ± 3.6
Phase 1 - Positive Score - Change-1.8 ± 1.8-0.81 ± 2.7
Phase 2 - Positive Score - Day 1420.7 ± 3.621.8 ± 3.6
Phase 2 - Positive Score - Day 2821.3 ± 4.622.3 ± 3.4
Phase 2 - Positive Score - Change0.5 ± 3.80.5 ± 2.17
Statistical analysis
  • Drug vs Placebo · ANCOVA · p = 0.35 (Exploratory efficacy outcome, hence no adjustment for multiple comparison.) · Mean difference (final values): -0.62
  • Drug vs Placebo · ANCOVA · p = 0.37 (Exploratory efficacy outcome, hence no adjustment for multiple comparisons) · Mean difference (final values): -0.62
SecondaryPANSS - Negative Subscale - Phases 1 and 2

The Positive and Negative Syndrome Scale (PANSS) will be used to measure symptom severity in this trial. PANSS is a 30-item questionnaire used to evaluate schizophrenia symptoms, based on the clinical interview as well as reports of family members or primary care hospital workers. PANSS consists of Positive scale (7 items), Negative scale (7 items), and General Psychopathological scale (16 items) sections. Each item (symptom) will be scored on a 7-point scale with higher scores representing increasing levels of psychopathology: 1) Absent, 2) Minimal, 3) Mild, 4) Moderate, 5) Moderate severe, 6) Severe, and 7) Extreme. Negative scale: 7 Items, (minimum score = 7, maximum score = 49)

Time frame:
Phase 1 timeframe is Day 0 and Day 14; Phase 2 timeframe is Day 14 and Day 28
Reported as:
Mean · units on a scale
PANSS - Negative Subscale - Phases 1 and 2
units on a scaleDrugPlacebo - Placebo
Phase 1 - Negative Score - Baseline20.8 ± 5.820.6 ± 4.8
Phase 1 - Negative Score - Day 1419.0 ± 4.619.7 ± 5.1
Phase 1 - Negative Score - Change-1.8 ± 4.1-1.0 ± 2.8
Phase 2 - Negative Score - Day 1418.5 ± 5.820.7 ± 4.4
Phase 2 - Negative Score - Day 2818.0 ± 6.219.8 ± 4.7
Phase 2 - Negative Score - Change-0.1 ± 0.9-0.9 ± 2.9
Statistical analysis
  • Drug vs Placebo - Placebo · ANCOVA · p = 0.85 · Mean difference (final values): -0.12
  • Drug vs Placebo - Placebo · ANCOVA · p = 0.88 · Mean difference (final values): -0.10
SecondaryPANSS - General Psychopathology Subscale - Phases 1 and 2

The Positive and Negative Syndrome Scale (PANSS) will be used to measure symptom severity in this trial. PANSS is a 30-item questionnaire used to evaluate schizophrenia symptoms, based on the clinical interview as well as reports of family members or primary care hospital workers. PANSS consists of Positive scale (7 items), Negative scale (7 items), and General Psychopathological scale (16 items) sections. Each item (symptom) will be scored on a 7-point scale with higher scores representing increasing levels of psychopathology: 1) Absent, 2) Minimal, 3) Mild, 4) Moderate, 5) Moderate severe, 6) Severe, and 7) Extreme. General Psychopathology Subscale: 16 Items, (minimum score = 16, maximum score = 112)

Time frame:
Phase 1 timeframe is Baseline and Day 14; Phase 2 timeframe is Day 14 and Day 28
Reported as:
Mean · units on a scale
PANSS - General Psychopathology Subscale - Phases 1 and 2
units on a scaleDrugPlacebo - Placebo
Phase 1 - General Score - Baseline37.6 ± 6.036.4 ± 5.1
Phase 1 - General Score - Day 1435.3 ± 7.135.5 ± 6.4
Phase 1 - General Score - Change-2.2 ± 7.0-0.6 ± 3.9
Phase 2 - General Score - Day 1434.7 ± 6.436.2 ± 6.6
Phase 2 - General Score - Day 2832.4 ± 5.632.4 ± 5.3
Phase 2 - General Score - Change-2.1 ± 5.2-3.7 ± 4.5
Statistical analysis
  • Drug vs Placebo - Placebo · ANCOVA · p = 0.86 · Mean difference (final values): -0.19
  • Drug vs Placebo - Placebo · ANCOVA · p = 0.83 · Mean difference (final values): -0.23
SecondaryAverage Percent Change From Baseline in the PANSS Total Score After 2 Weeks of Treatment Using SPCD

The Positive and Negative Syndrome Scale (PANSS) will be used to measure symptom severity in this trial. PANSS is a 30-item questionnaire used to evaluate schizophrenia symptoms, based on the clinical interview as well as reports of family members or primary care hospital workers. PANSS consists of Positive scale (7 items), Negative scale (7 items), and General Psychopathological scale (16 items) sections. Each item (symptom) will be scored on a 7-point scale with higher scores representing increasing levels of psychopathology: 1) Absent, 2) Minimal, 3) Mild, 4) Moderate, 5) Moderate severe, 6) Severe, and 7) Extreme. Total score minimum = 30, maximum = 210.

Time frame:
For Phase 1, timeframe is Baseline and Day 14; Phase 2 timeframe is Day 14 and Day 28
Reported as:
Mean · percent change
Average Percent Change From Baseline in the PANSS Total Score After 2 Weeks of Treatment Using SPCD
percent changeDrugPlacebo
Phase 1 Average Percent Change from Baseline-6.7 ± 12.8-3.2 ± 9.0
Phase 2 Average Percentage Change from Day 14-3.0 ± 10.5-3.3 ± 8.1
SecondaryPercentage of Subjects With 20% or More Reduction From Baseline in PANSS Total Score After 2 Weeks of Treatment Using SPCD

The Positive and Negative Syndrome Scale (PANSS) will be used to measure symptom severity in this trial. PANSS is a 30-item questionnaire used to evaluate schizophrenia symptoms, based on the clinical interview as well as reports of family members or primary care hospital workers. PANSS consists of Positive scale (7 items), Negative scale (7 items), and General Psychopathological scale (16 items) sections. Each item (symptom) will be scored on a 7-point scale with higher scores representing increasing levels of psychopathology: 1) Absent, 2) Minimal, 3) Mild, 4) Moderate, 5) Moderate severe, 6) Severe, and 7) Extreme. Total score minimum = 30, maximum = 210.

Time frame:
For Phase 1, timeframe is Baseline and Day 14; Phase 2 timeframe is Day 14 and Day 28
Reported as:
Number · percent of subjects
Percentage of Subjects With 20% or More Reduction From Baseline in PANSS Total Score After 2 Weeks of Treatment Using SPCD
percent of subjectsDrugPlacebo
Phase 1 % of subjects with >=20% reduction16.670
Phase 2 % of subjects with >=20% reduction05.56
SecondaryAverage Percent Change From Baseline in the PANSS Positive Subscale Score After 2 Weeks of Treatment Using SPCD

The Positive and Negative Syndrome Scale (PANSS) will be used to measure symptom severity in this trial. PANSS is a 30-item questionnaire used to evaluate schizophrenia symptoms, based on the clinical interview as well as reports of family members or primary care hospital workers. PANSS consists of Positive scale (7 items), Negative scale (7 items), and General Psychopathological scale (16 items) sections. Each item (symptom) will be scored on a 7-point scale with higher scores representing increasing levels of psychopathology: 1) Absent, 2) Minimal, 3) Mild, 4) Moderate, 5) Moderate severe, 6) Severe, and 7) Extreme. Positive subscore scale: 7 items (minimum score = 7; maximum score = 49)

Time frame:
For Phase 1, timeframe is Baseline and Day 14; Phase 2 timeframe is Day 14 and Day 28
Reported as:
Mean · percent change
Average Percent Change From Baseline in the PANSS Positive Subscale Score After 2 Weeks of Treatment Using SPCD
percent changeDrugPlacebo
Phase 1 Average Percent Change from Baseline-7.9 ± 8.1-3.2 ± 13.6
Phase 2 Average Percentage Change from Day 14-3.5 ± 15.4-2.9 ± 12.5
SecondaryAverage Percent Change From Baseline in the PANSS Negative Subscale Score After 2 Weeks of Treatment Using SPCD

The Positive and Negative Syndrome Scale (PANSS) will be used to measure symptom severity in this trial. PANSS is a 30-item questionnaire used to evaluate schizophrenia symptoms, based on the clinical interview as well as reports of family members or primary care hospital workers. PANSS consists of Positive scale (7 items), Negative scale (7 items), and General Psychopathological scale (16 items) sections. Each item (symptom) will be scored on a 7-point scale with higher scores representing increasing levels of psychopathology: 1) Absent, 2) Minimal, 3) Mild, 4) Moderate, 5) Moderate severe, 6) Severe, and 7) Extreme. Negative subscore scale: 7 items (minimum score = 7; maximum score = 49)

Time frame:
For Phase 1, timeframe is Baseline and Day 14; Phase 2 timeframe is Day 14 and Day 28
Reported as:
Mean · percent change
Average Percent Change From Baseline in the PANSS Negative Subscale Score After 2 Weeks of Treatment Using SPCD
percent changeDrugPlacebo
Phase 1 Average Percent Change from Baseline-7.1 ± 17.6-4.6 ± 14.9
Phase 2 Average Percentage Change from Day 14-7.9 ± 12.3-2.1 ± 16.5
SecondaryAverage Percent Change From Baseline in the PANSS General Psychopathology Subscale Score After 2 Weeks of Treatment Using SPCD

The Positive and Negative Syndrome Scale (PANSS) will be used to measure symptom severity in this trial. PANSS is a 30-item questionnaire used to evaluate schizophrenia symptoms, based on the clinical interview as well as reports of family members or primary care hospital workers. PANSS consists of Positive scale (7 items), Negative scale (7 items), and General Psychopathological scale (16 items) sections. Each item (symptom) will be scored on a 7-point scale with higher scores representing increasing levels of psychopathology: 1) Absent, 2) Minimal, 3) Mild, 4) Moderate, 5) Moderate severe, 6) Severe, and 7) Extreme. General Psychopathology subscore scale: 16 items (minimum score = 16; maximum score = 112)

Time frame:
For Phase 1, timeframe is Baseline and Day 14; Phase 2 timeframe is Day 14 and Day 28
Reported as:
Mean · percent change
Average Percent Change From Baseline in the PANSS General Psychopathology Subscale Score After 2 Weeks of Treatment Using SPCD
percent changeDrugPlacebo
Phase 1 Average Percent Change from Baseline-4.8 ± 18.3-1.8 ± 10.9
Phase 2 Average Percentage Change from Day 140.47 ± 13.3-3.7 ± 8.7
Other pre-specifiedChange in the Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Consensus Cognitive Battery (MCCB) - Phases 1 and 2

MATRICS: The Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Consensus Cognitive Battery (MCCB). The MATRICS Consensus Cognitive Battery is the standard tool for assessing cognitive change in trials of cognitive-enhancing agents in schizophrenia. The MCCB domains include: Speed of Processing; Attention/Vigilance; Working Memory; Verbal Learning; Visual Learning; Reasoning \& Problem-Solving; and Social Cognition and the battery takes about 80 minutes to complete. The MCCB composite score represents a global measure of cognition. MCCB composite T scores are between 40 and 60 (normal range) and \< 40 (below normal range).

Time frame:
Phase 1 timeframe is Baseline and Day 14; Phase 2 timeframe is Day 14 and Day 28
Reported as:
Mean · T-scores
Change in the Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Consensus Cognitive Battery (MCCB) - Phases 1 and 2
T-scoresDrugPlacebo - Placebo
Phase 1 - Baseline26.2 ± 14.326.5 ± 14.5
Phase 1 - Day 1429.3 ± 12.928.6 ± 16.2
Phase 1 - Change3.1 ± 3.91.4 ± 5.1
Phase 2 - Day 1428.8 ± 12.828.4 ± 18.8
Phase 2 - Day 2830.3 ± 13.631.0 ± 18.0
Phase 2 - Change3.3 ± 4.22.6 ± 5.2
Statistical analysis
  • Drug vs Placebo - Placebo · ANCOVA · p = 0.33 · Mean difference (final values): 1.12
  • Drug vs Placebo - Placebo · ANCOVA · p = 0.34 · Mean difference (final values): 1.10
Other pre-specifiedAverage AIMS Total Scores (Items 1-7) by Group and Timepoint

Abnormal Involuntary Movement Scale (AIMS): The AIMS Total Dyskinesia Score was calculated by averaging the first 7 items of the AIMS. The 7 items included in the AIMS Dyskinesia Score are rated on a scale from 0 (no dyskinesia) to 4 (severe dyskinesia). Items 1 through 7 include facial and oral movements (Items 1-4), extremity movements (Items 5-6), and trunk movements (Item 7). The AIMS dyskinesia total score ranges from 0 to 4; a higher score reflects increased severity.

Time frame:
Baseline 1 (Day -1), 7 Hours Post-Infusion 1, Baseline 2 (Day 13), 7 Hours Post-Infusion 2, Final Follow-Up, including early termination visits
Reported as:
Mean · units on a scale
Average AIMS Total Scores (Items 1-7) by Group and Timepoint
units on a scaleDrug - DrugPlacebo - DrugPlacebo - Placebo
Baseline 10.72 ± 1.410.56 ± 0.960.56 ± 0.96
7 Hours Post-Infusion 10.56 ± 1.100.31 ± 0.480.31 ± 0.48
Baseline 20.44 ± 0.921.00 ± 1.471.00 ± 1.47
7 Hours Post-Infusion 20.47 ± 0.870.54 ± 0.880.54 ± 0.88
Final follow-up1.00 ± 2.090.93 ± 1.670.93 ± 1.67
Other pre-specifiedPercent of Participants Rated as ≥ "Mild" or as "Yes" on AIMS Items 8-12

Abnormal Involuntary Movement Scale (AIMS): The AIMS is a 12-item anchored score that is clinician administered and scored. Items are scored on a 0 (none) to 4 (severe) basis; items 8-10 deal with global severity; items 11-12 are yes-no questions concerning problems with teeth and/or dentures.

Time frame:
Baseline (Day -1), Follow-Up = reported at any assessment thereafter, including 7 hours after Infusions #1 and #2, Baseline 2 (Day 13) and final follow-up, including early termination visits.
Reported as:
Number · percentage of participants
Percent of Participants Rated as ≥ "Mild" or as "Yes" on AIMS Items 8-12
percentage of participantsDrug - DrugPlacebo - DrugPlacebo - Placebo
Baseline - Overall Severity Index (Item 8)5.66.311.1
Follow-Up - Overall Severity Index (Item 8)16.718.816.7
Baseline - Incapacitation (Item 9)0.00.05.6
Follow-Up - Incapacitation (Item 9)0.06.30.0
Baseline - Awareness (Item 10)11.16.35.6
Follow-Up - Awareness (Item 10)5.618.85.6
Baseline - Dental Problem (Item 11; % yes)22.231.316.7
Follow-Up - Dental Problem (Item 11; % yes)27.837.522.2
Baseline - Dentures (Item 12; % yes)5.618.816.7
Follow-Up - Dentures (Item 12; % yes)11.131.322.2
Other pre-specifiedChange in The University of California San Diego (UCSD) Performance-based Skills Assessment Brief (UPSA-B) - Phases 1 and 2

The University of California San Diego (UCSD) Performance-based Skills Assessment Brief (UPSA-B) consists of two of the five original UPSA domains, finances and communication. Each subscale contributes 50 points; total scores range from 0 to 100 points with higher scores reflecting better performance.

Time frame:
Phase 1 timeframe is Baseline and Day 14; Phase 2 timeframe is Day 14 and Day 28
Reported as:
Mean · units on a scale
Change in The University of California San Diego (UCSD) Performance-based Skills Assessment Brief (UPSA-B) - Phases 1 and 2
units on a scaleDrugPlacebo - Placebo
Phase 1 - Baseline74.0 ± 17.271.8 ± 17.1
Phase 1 - Day 1476.7 ± 17.477.9 ± 14.6
Phase 1 - Change2.7 ± 7.66.2 ± 9.9
Phase 2 - Day 1480.2 ± 13.176.0 ± 15.9
Phase 2 - Day 2885.4 ± 11.274.5 ± 20.9
Phase 2 - Change5.5 ± 7.7-1.5 ± 10.9
Statistical analysis
  • Drug vs Placebo - Placebo · ANCOVA · p = 0.34 · Mean difference (final values): 1.11
  • Drug vs Placebo - Placebo · ANCOVA · p = 0.36 · Mean difference (final values): 2.05
Other pre-specifiedNumber of Participants Reporting Suicidal Ideation/Behavior on the Columbia Suicide Severity Rating Scale (C-SSRS)

The Columbia Suicide Severity Rating Scale (C-SSRS): The C-SSRS is a low-burden measure of the spectrum of suicidal ideation and behavior that was developed in the National Institute of Mental Health Treatment of Adolescent Suicide Attempters Study to assess severity and track suicidal events through any treatment. It is a clinical interview providing a summary of both ideation and behavior that can be administered during any evaluation or risk assessment to identify the level and type of suicidality present. The C-SSRS can also be used during treatment to monitor for clinical worsening or improvement. It contains 5 rating scale questions (yes/no) for suicidal ideation increasing severity and 5 rating scale questions (yes/no) for suicidal behavior of increasing severity. The time frame is for both lifetime and the past six months for the Baseline/Screening scale and since the last visit for the Since Last Visit scale.

Time frame:
Screening Visit, Days 3 (Baseline 1), Days 7, 13 (Baseline 2), 21 and 28
Reported as:
Count of participants · Participants
Number of Participants Reporting Suicidal Ideation/Behavior on the Columbia Suicide Severity Rating Scale (C-SSRS)
ParticipantsDrug - DrugPlacebo - DrugPlacebo - Placebo
Suicidal ideation (SI) (% any of the following)212
Wish to be dead111
Non-specific active suicidal thoughts211
Active SI w/any method (no plan) W/O intent to act000
Active SI w/some intent to act, W/O specific plan000
Active SI with specific plan & intent000
Suicidal behavior (% any of the following)000
Prepatory acts or behavior000
Aborted attempt000
Interrupted attempt000
Non-fatal suicide attempt000
Self-injurious behavior W/O suicidal intent000
Other pre-specifiedSystolic Blood Pressure Per Infusion Phase by Group

Infusion 1 (Day 0) - Systolic Blood Pressure at all time points by group "Phase" in this analysis refers to the infusion stage as defined in the protocol.

Time frame:
Day 0 - Phase 1 - Baseline = min000s1 and @5 min; Phase 2 - Baseline = min000 then every 10 minutes for 4 hours; Post Infusion - Baseline = min000, then every 10 minutes for 2 hours
Reported as:
Mean · mmHg
Systolic Blood Pressure Per Infusion Phase by Group
mmHgDrug-DrugPlacebo-DrugPlacebo - Placebo
Phase 1 - min000s1121.79 ± 14.46121.50 ± 10.65123.78 ± 11.46
Phase 1 - min005s1116.95 ± 12.78126.13 ± 13.01121.94 ± 14.39
Phase 2 - min000114.89 ± 13.13125.13 ± 11.04121.00 ± 12.86
Phase 2 - min005111.32 ± 11.51124.38 ± 10.29121.00 ± 14.12
Phase 2 - min010112.72 ± 12.84127.06 ± 8.93122.33 ± 11.56
Phase 2 - min015111.28 ± 9.48125.75 ± 10.51121.94 ± 11.58
Phase 2 - min020108.28 ± 10.21124.63 ± 9.94121.11 ± 10.81
Phase 2 - min025109.83 ± 10.70126.63 ± 11.89121.11 ± 11.80
Phase 2 - min030108.61 ± 10.01125.13 ± 9.84119.67 ± 13.77
Phase 2 - min040111.82 ± 9.80125.63 ± 11.86122.56 ± 11.46
Phase 2 - min050111.00 ± 8.89125.73 ± 9.32122.56 ± 11.46
Phase 2 - min060112.53 ± 11.99126.87 ± 9.69120.17 ± 12.91
Phase 2 - min070114.82 ± 12.83126.27 ± 8.86120.11 ± 10.76
Phase 2 - min080110.00 ± 9.98125.53 ± 9.62120.83 ± 13.90
Phase 2 - min090111.94 ± 9.83125.00 ± 11.14121.33 ± 12.88
Phase 2 - min100111.00 ± 12.97123.87 ± 11.75122.11 ± 12.39
Phase 2 - min110112.29 ± 7.83128.33 ± 10.60122.83 ± 12.32
Phase 2 - min120111.76 ± 10.56124.93 ± 12.57119.06 ± 15.30
Phase 2 - min130109.82 ± 9.19125.20 ± 8.99119.17 ± 10.63
Phase 2 - min140109.47 ± 7.34127.67 ± 9.76119.72 ± 11.20
Phase 2 - min150110.12 ± 9.62126.93 ± 10.75123.39 ± 12.95
Phase 2 - min160107.88 ± 9.97126.00 ± 9.56121.72 ± 15.23
Phase 2 - min170109.35 ± 11.89124.33 ± 9.51122.72 ± 15.14
Phase 2 - min180110.06 ± 9.85127.07 ± 12.63123.22 ± 13.01
Phase 2 - min190110.12 ± 11.60125.13 ± 13.10121.94 ± 12.46
Phase 2 - min200107.41 ± 12.57125.40 ± 13.00122.67 ± 14.63
Phase 2 - min210109.71 ± 8.08131.87 ± 13.79122.94 ± 11.34
Phase 2 - min220109.82 ± 9.57125.73 ± 13.24125.89 ± 14.58
Phase 2 - min230109.35 ± 9.57126.00 ± 13.80124.61 ± 13.75
Phase 2 - min240109.53 ± 9.13128.67 ± 14.01124.44 ± 14.16
Post Infusion - min000107.50 ± 11.53128.38 ± 13.87125.22 ± 13.80
Post Infusion - min005114.44 ± 11.01126.13 ± 13.84123.12 ± 10.01
Post Infusion - min010116.28 ± 11.74127.33 ± 12.80122.06 ± 11.62
Post Infusion - min015117.22 ± 11.07128.40 ± 16.79124.67 ± 11.96
Post Infusion - min020117.39 ± 9.12128.80 ± 13.04124.50 ± 12.08
Post Infusion - min025116.33 ± 12.58129.53 ± 14.94126.72 ± 14.74
Post Infusion - min030118.56 ± 11.93129.81 ± 13.96124.00 ± 14.12
Post Infusion - min040119.67 ± 12.03128.33 ± 14.99123.33 ± 14.48
Post Infusion - min050117.33 ± 13.91128.47 ± 11.86123.11 ± 13.78
Post Infusion - min060122.22 ± 12.35129.93 ± 12.21124.61 ± 14.97
Post Infusion - min070122.33 ± 13.78130.27 ± 11.51122.72 ± 15.86
Post Infusion - min080118.83 ± 12.78128.47 ± 11.86122.94 ± 14.49
Post Infusion - min090117.67 ± 12.56129.20 ± 13.03124.06 ± 10.94
Post Infusion - min100120.44 ± 11.87125.67 ± 11.63121.72 ± 10.65
Post Infusion - min110122.61 ± 13.42129.27 ± 11.49125.06 ± 14.58
Post Infusion - min120122.22 ± 13.41128.67 ± 10.99124.44 ± 12.34
Other pre-specifiedDiastolic Blood Pressure Per Infusion Phase by Group

Infusion 1 (Day 0) - Diastolic Blood Pressure at all time points by group "Phase" in this analysis refers to the infusion stage as defined in the protocol.

Time frame:
Day 0 - Phase 1 - Baseline = min000s1 and @5 min; Phase 2 - Baseline = min000 then every 10 minutes for 4 hours; Post Infusion - Baseline = min000, then every 10 minutes for 2 hours
Reported as:
Mean · mmHg
Diastolic Blood Pressure Per Infusion Phase by Group
mmHgDrug-DrugPlacebo-DrugPlacebo - Placebo
Phase 1 - min000s171.63 ± 19.0375.13 ± 10.4475.11 ± 10.12
Phase 1 - min005s168.79 ± 10.1275.38 ± 6.3074.94 ± 9.91
Phase 2 - min00067.58 ± 10.1874.44 ± 7.2874.72 ± 11.88
Phase 2 - min00566.37 ± 12.8874.31 ± 7.0174.39 ± 8.42
Phase 2 - min01065.72 ± 14.7075.50 ± 8.0973.72 ± 9.50
Phase 2 - min01562.67 ± 9.9474.75 ± 8.3872.78 ± 8.61
Phase 2 - min02062.06 ± 9.3375.19 ± 8.2974.33 ± 12.25
Phase 2 - min02562.33 ± 8.6174.31 ± 6.0272.83 ± 11.20
Phase 2 - min03060.78 ± 8.9375.50 ± 8.0972.06 ± 11.67
Phase 2 - min04061.29 ± 7.4675.06 ± 9.7672.67 ± 11.66
Phase 2 - min05060.65 ± 7.5276.47 ± 10.2371.28 ± 10.06
Phase 2 - min06061.88 ± 9.5075.80 ± 9.3071.94 ± 11.11
Phase 2 - min07064.53 ± 11.2175.27 ± 9.6271.11 ± 12.74
Phase 2 - min08062.41 ± 10.8976.73 ± 9.8071.61 ± 11.69
Phase 2 - min09064.18 ± 11.4874.53 ± 9.8173.11 ± 14.06
Phase 2 - min10062.29 ± 8.9674.87 ± 7.7473.94 ± 11.50
Phase 2 - min11063.94 ± 6.9777.07 ± 12.0272.06 ± 12.98
Phase 2 - min12066.94 ± 12.0274.20 ± 8.9472.28 ± 14.71
Phase 2 - min13062.47 ± 8.8776.27 ± 8.4469.72 ± 13.47
Phase 2 - min14061.94 ± 8.7578.27 ± 8.9671.06 ± 10.98
Phase 2 - min15064.53 ± 6.3875.60 ± 8.1073.83 ± 11.74
Phase 2 - min16061.88 ± 8.9975.53 ± 17.0172.22 ± 10.50
Phase 2 - min17062.29 ± 6.2874.40 ± 9.3072.83 ± 11.74
Phase 2 - min18062.06 ± 9.0574.20 ± 9.6772.22 ± 12.74
Phase 2 - min19063.47 ± 9.4174.67 ± 7.4873.56 ± 11.93
Phase 2 - min20064.18 ± 7.5778.60 ± 9.8374.33 ± 11.63
Phase 2 - min21063.82 ± 9.5176.20 ± 8.8375.56 ± 11.22
Phase 2 - min22063.47 ± 10.4076.00 ± 9.0675.17 ± 12.94
Phase 2 - min23060.82 ± 9.1376.40 ± 7.9574.17 ± 9.82
Phase 2 - min24063.47 ± 8.4676.53 ± 7.7974.00 ± 10.19
Post Infusion - min00062.56 ± 8.6977.50 ± 8.4074.67 ± 11.11
Post Infusion - min00567.17 ± 9.6776.40 ± 8.4976.18 ± 9.19
Post Infusion - min01066.78 ± 9.9078.07 ± 9.0375.56 ± 13.17
Post Infusion - min01569.00 ± 10.8476.20 ± 9.6575.78 ± 11.33
Post Infusion - min02071.72 ± 11.1077.80 ± 12.2575.61 ± 12.53
Post Infusion - min02566.72 ± 11.4078.87 ± 10.8077.06 ± 10.80
Post Infusion - min03069.67 ± 9.0078.81 ± 9.7075.33 ± 11.75
Post Infusion - min04068.06 ± 11.4377.53 ± 10.8575.89 ± 11.84
Post Infusion - min05069.56 ± 10.7878.40 ± 7.2775.17 ± 11.81
Post Infusion - min06068.83 ± 10.4479.33 ± 11.1774.61 ± 10.87
Post Infusion - min07070.22 ± 10.3378.13 ± 7.4975.28 ± 9.37
Post Infusion - min08071.89 ± 10.0276.60 ± 7.4975.06 ± 13.17
Post Infusion - min09069.89 ± 7.0879.07 ± 9.0674.44 ± 10.07
Post Infusion - min10069.50 ± 9.2476.80 ± 10.7573.56 ± 10.61
Post Infusion - min11071.61 ± 8.1376.53 ± 10.6474.22 ± 9.74
Post Infusion - min12070.61 ± 9.8678.27 ± 8.4075.89 ± 8.53
Other pre-specifiedSystolic Blood Pressure Per Infusion Phase by Group

Infusion 2 (Day 14) - Systolic Blood Pressure at all time points by group "Phase" in this analysis refers to the infusion stage as defined in the protocol.

Time frame:
Day 14 - Phase 1 - Baseline = min000s1 and @5 min; Phase 2 - Baseline = min000 then every 10 minutes for 4 hours; Post Infusion - Baseline = min000, then every 10 minutes for 2 hours
Reported as:
Mean · mmHg
Systolic Blood Pressure Per Infusion Phase by Group
mmHgDrug-DrugPlacebo-DrugPlacebo - Placebo
Phase 1 - min000s1120.69 ± 11.84121.92 ± 9.66122.61 ± 10.22
Phase 1 - min005s1112.69 ± 12.38120.77 ± 12.38119.39 ± 10.67
Phase 2 - min000110.88 ± 11.61120.92 ± 14.20120.78 ± 12.08
Phase 2 - min005107.50 ± 11.36116.31 ± 9.96120.39 ± 12.22
Phase 2 - min010108.50 ± 9.39113.38 ± 12.53120.41 ± 12.62
Phase 2 - min015108.88 ± 9.06113.46 ± 10.32117.28 ± 13.35
Phase 2 - min020108.19 ± 8.93112.62 ± 10.66117.94 ± 12.65
Phase 2 - min025110.81 ± 11.11115.62 ± 13.88118.22 ± 14.40
Phase 2 - min030109.88 ± 8.43113.69 ± 16.09116.44 ± 13.40
Phase 2 - min040108.06 ± 8.46117.54 ± 16.58118.94 ± 11.57
Phase 2 - min050109.00 ± 10.22112.77 ± 13.91118.56 ± 15.60
Phase 2 - min060109.63 ± 13.20113.31 ± 14.12116.94 ± 12.75
Phase 2 - min070108.56 ± 10.46113.15 ± 12.15118.50 ± 14.20
Phase 2 - min080108.50 ± 10.98113.08 ± 15.34118.50 ± 13.57
Phase 2 - min090109.06 ± 10.59109.00 ± 11.63118.06 ± 12.49
Phase 2 - min100106.94 ± 11.58111.50 ± 16.10119.00 ± 14.98
Phase 2 - min110105.67 ± 7.80112.46 ± 16.04120.39 ± 11.95
Phase 2 - min120105.87 ± 9.19106.33 ± 10.87118.83 ± 15.25
Phase 2 - min130108.53 ± 10.70110.17 ± 11.75120.06 ± 13.58
Phase 2 - min140111.27 ± 10.50110.54 ± 11.23120.33 ± 15.11
Phase 2 - min150112.13 ± 11.42110.83 ± 18.52117.67 ± 12.76
Phase 2 - min160109.87 ± 11.11116.17 ± 13.07121.17 ± 13.79
Phase 2 - min170114.33 ± 12.61113.33 ± 12.04120.61 ± 12.65
Phase 2 - min180111.27 ± 9.38113.92 ± 11.77117.67 ± 11.44
Phase 2 - min190110.47 ± 9.82114.83 ± 16.46120.72 ± 11.74
Phase 2 - min200110.40 ± 13.47115.08 ± 16.76120.94 ± 14.24
Phase 2 - min210113.13 ± 14.71114.33 ± 17.85121.17 ± 11.75
Phase 2 - min220109.20 ± 15.18112.33 ± 11.54120.06 ± 11.44
Phase 2 - min230110.27 ± 12.79113.58 ± 12.92118.83 ± 12.64
Phase 2 - min240108.53 ± 9.48111.83 ± 12.58119.00 ± 12.29
Post Infusion - min000107.75 ± 9.94113.25 ± 13.51118.22 ± 120.28
Post Infusion - min005111.06 ± 12.41118.25 ± 18.23120.28 ± 11.93
Post Infusion - min010116.88 ± 16.70122.83 ± 16.03122.94 ± 10.91
Post Infusion - min015114.75 ± 15.07124.58 ± 16.14122.78 ± 11.70
Post Infusion - min020115.00 ± 11.55122.92 ± 13.24121.56 ± 12.60
Post Infusion - min025116.00 ± 12.41125.83 ± 16.94126.67 ± 15.06
Post Infusion - min030117.50 ± 12.56123.67 ± 16.54126.06 ± 14.86
Post Infusion - min040118.44 ± 11.40123.92 ± 11.24122.11 ± 13.75
Post Infusion - min050122.75 ± 22.66124.17 ± 13.19122.72 ± 14.82
Post Infusion - min060125.31 ± 14.93121.08 ± 12.45123.17 ± 15.00
Post Infusion - min070122.44 ± 19.68120.33 ± 10.46124.78 ± 14.82
Post Infusion - min080122.38 ± 15.21121.83 ± 14.65123.17 ± 13.34
Post Infusion - min090122.25 ± 14.19125.08 ± 13.73126.28 ± 14.52
Post Infusion - min100121.94 ± 21.68123.92 ± 10.99122.94 ± 16.25
Post Infusion - min110123.50 ± 13.57125.17 ± 16.51125.06 ± 11.88
Post Infusion - min120122.31 ± 16.41125.75 ± 12.26125.00 ± 12.29
Other pre-specifiedPhase 2 - Diastolic Blood Pressure Per Infusion Phase by Group

Infusion 2 (Day 14) - Diastolic Blood Pressure at all time points by group

Time frame:
Day 14 - Phase 1 - Baseline = min000s1 and @5 min; Phase 2 - Baseline = min000 then every 10 minutes for 4 hours; Post Infusion - Baseline = min000, then every 10 minutes for 2 hours
Reported as:
Mean · mmHg
Phase 2 - Diastolic Blood Pressure Per Infusion Phase by Group
mmHgDrug-DrugPlacebo-DrugPlacebo - Placebo
Phase 1 - min000s169.38 ± 7.8074.50 ± 8.8974.50 ± 8.89
Phase 1 - min005s163.56 ± 8.7873.89 ± 8.7073.89 ± 8.70
Phase 2 - min00063.94 ± 8.4672.72 ± 8.8472.72 ± 8.84
Phase 2 - min00561.00 ± 6.2371.28 ± 7.2871.28 ± 7.28
Phase 2 - min01061.63 ± 7.5774.65 ± 9.0374.65 ± 9.03
Phase 2 - min01561.44 ± 9.0673.50 ± 7.1573.50 ± 7.15
Phase 2 - min02063.19 ± 8.7270.94 ± 7.0770.94 ± 7.07
Phase 2 - min02559.25 ± 8.2971.56 ± 9.1071.56 ± 9.10
Phase 2 - min03061.75 ± 7.8771.11 ± 7.2371.11 ± 7.23
Phase 2 - min04059.94 ± 8.8273.17 ± 9.0773.17 ± 9.07
Phase 2 - min05060.25 ± 8.4271.89 ± 12.0771.89 ± 12.07
Phase 2 - min06060.38 ± 11.9771.44 ± 12.2371.44 ± 12.23
Phase 2 - min07059.19 ± 10.7871.00 ± 10.7771.00 ± 10.77
Phase 2 - min08059.00 ± 7.3870.72 ± 12.8170.72 ± 12.81
Phase 2 - min09057.13 ± 7.8370.22 ± 12.3470.22 ± 12.34
Phase 2 - min10058.13 ± 8.3771.00 ± 12.3971.00 ± 12.39
Phase 2 - min11059.73 ± 5.9771.89 ± 11.5471.89 ± 11.54
Phase 2 - min12059.47 ± 8.5968.28 ± 10.6568.28 ± 10.65
Phase 2 - min13060.33 ± 8.1673.44 ± 11.9473.44 ± 11.94
Phase 2 - min14058.73 ± 10.2371.56 ± 10.8771.56 ± 10.87
Phase 2 - min15061.87 ± 10.1074.06 ± 12.8074.06 ± 12.80
Phase 2 - min16060.53 ± 7.6873.94 ± 10.4173.94 ± 10.41
Phase 2 - min17061.87 ± 11.6074.61 ± 8.4374.61 ± 8.43
Phase 2 - min18060.27 ± 9.0072.28 ± 8.1772.28 ± 8.17
Phase 2 - min19059.73 ± 10.2373.00 ± 10.9973.00 ± 10.99
Phase 2 - min20058.40 ± 7.0373.56 ± 10.3573.56 ± 10.35
Phase 2 - min21060.27 ± 9.0074.11 ± 11.5374.11 ± 11.53
Phase 2 - min22059.13 ± 8.6072.22 ± 9.6272.22 ± 9.62
Phase 2 - min23062.00 ± 8.1272.33 ± 10.4872.33 ± 10.48
Phase 2 - min24059.60 ± 8.5870.11 ± 8.0570.11 ± 8.05
Post Infusion - min00059.81 ± 8.4270.39 ± 8.1070.39 ± 8.10
Post Infusion - min00563.31 ± 7.8771.94 ± 9.1471.94 ± 9.14
Post Infusion - min01067.06 ± 9.2673.39 ± 9.7673.39 ± 9.76
Post Infusion - min01565.13 ± 10.2075.67 ± 10.7975.67 ± 10.79
Post Infusion - min02069.44 ± 12.4474.89 ± 9.6274.89 ± 8.66
Post Infusion - min02566.88 ± 12.9476.89 ± 8.6676.89 ± 8.66
Post Infusion - min03068.81 ± 12.4576.89 ± 14.5776.89 ± 14.57
Post Infusion - min04070.31 ± 14.8972.39 ± 11.3272.39 ± 11.32
Post Infusion - min05070.25 ± 10.7974.72 ± 12.5674.72 ± 12.56
Post Infusion - min06067.69 ± 7.8874.11 ± 11.9074.11 ± 11.90
Post Infusion - min07068.81 ± 9.7276.78 ± 10.2876.78 ± 10.28
Post Infusion - min08068.88 ± 7.8774.61 ± 11.2574.61 ± 11.25
Post Infusion - min09069.88 ± 8.8773.83 ± 11.4073.83 ± 11.40
Post Infusion - min10069.38 ± 8.6174.28 ± 12.1574.28 ± 12.15
Post Infusion - min11070.81 ± 9.0977.11 ± 10.7877.11 ± 10.78
Post Infusion - min12070.56 ± 7.6978.00 ± 9.1578.00 ± 9.15
Other pre-specifiedHeart Rate Per Infusion Phase by Group

Infusion 1 (Day 0) - Heart rate at all time points by group "Phase" in this analysis refers to the infusion stage as defined in the protocol.

Time frame:
Day 0 - Phase 1 - Baseline = min000s1 and @5 min; Phase 2 - Baseline = min000 then every 10 minutes for 4 hours; Post Infusion - Baseline = min000, then every 10 minutes for 2 hours
Reported as:
Mean · bpm
Heart Rate Per Infusion Phase by Group
bpmDrug-DrugPlacebo-DrugPlacebo - Placebo
Phase 1 - min000s178.47 ± 13.1179.00 ± 15.8479.94 ± 17.67
Phase 1 - min005s181.21 ± 15.7977.81 ± 14.3979.44 ± 16.33
Phase 2 - min00084.00 ± 13.8176.94 ± 15.0579.94 ± 16.86
Phase 2 - min00585.47 ± 13.4977.88 ± 15.1378.00 ± 17.19
Phase 2 - min01085.17 ± 13.4477.25 ± 14.7579.61 ± 16.75
Phase 2 - min01584.33 ± 13.9778.00 ± 14.0177.89 ± 17.33
Phase 2 - min02083.00 ± 13.8476.44 ± 14.7779.28 ± 17.28
Phase 2 - min02583.83 ± 14.6177.13 ± 13.6177.06 ± 17.12
Phase 2 - min03083.94 ± 14.2176.69 ± 14.3878.83 ± 17.57
Phase 2 - min04083.06 ± 13.9877.88 ± 14.4277.56 ± 18.10
Phase 2 - min05083.65 ± 14.2876.67 ± 13.2879.50 ± 18.06
Phase 2 - min06083.59 ± 13.8678.13 ± 12.8878.56 ± 17.12
Phase 2 - min07082.53 ± 13.7377.07 ± 12.6677.11 ± 17.27
Phase 2 - min08084.76 ± 13.3776.47 ± 15.0876.89 ± 17.83
Phase 2 - min09083.82 ± 12.7377.80 ± 14.3676.22 ± 17.13
Phase 2 - min10084.29 ± 12.4678.53 ± 12.8275.94 ± 16.31
Phase 2 - min11085.18 ± 12.5476.73 ± 11.6675.44 ± 16.76
Phase 2 - min12083.71 ± 11.9778.47 ± 13.5278.39 ± 20.37
Phase 2 - min13083.59 ± 12.5077.33 ± 12.6675.94 ± 15.69
Phase 2 - min14081.76 ± 11.9977.60 ± 12.7975.28 ± 16.35
Phase 2 - min15082.06 ± 13.3879.67 ± 11.7976.06 ± 15.42
Phase 2 - min16083.41 ± 11.4978.73 ± 11.8179.33 ± 16.11
Phase 2 - min17083.88 ± 11.1979.07 ± 13.5776.44 ± 18.07
Phase 2 - min18082.12 ± 10.3477.53 ± 13.7278.56 ± 16.76
Phase 2 - min19083.24 ± 12.4079.40 ± 15.0876.89 ± 16.36
Phase 2 - min20083.41 ± 11.3779.27 ± 13.4280.00 ± 15.98
Phase 2 - min21081.24 ± 11.6880.27 ± 14.3977.50 ± 15.57
Phase 2 - min22082.94 ± 12.2979.93 ± 14.1077.33 ± 16.83
Phase 2 - min23084.47 ± 12.9679.87 ± 15.0678.78 ± 16.75
Phase 2 - min24085.29 ± 12.0179.40 ± 13.7478.56 ± 16.85
Post Infusion - min00086.28 ± 11.9682.44 ± 14.8178.11 ± 16.91
Post Infusion - min00580.39 ± 12.4680.80 ± 15.8180.29 ± 16.13
Post Infusion - min01080.78 ± 12.7478.67 ± 131778.83 ± 14.77
Post Infusion - min01580.67 ± 10.3279.93 ± 13.3479.39 ± 15.79
Post Infusion - min02082.06 ± 10.7882.13 ± 13.9180.33 ± 16.94
Post Infusion - min02579.78 ± 11.8381.60 ± 13.8378.22 ± 17.13
Post Infusion - min03079.39 ± 13.5682.13 ± 13.0779.72 ± 16.44
Post Infusion - min04079.72 ± 12.5581.47 ± 13.4178.72 ± 15.97
Post Infusion - min05079.06 ± 12.3278.47 ± 13.4581.28 ± 15.18
Post Infusion - min06079.17 ± 11.9379.40 ± 12.4078.83 ± 15.96
Post Infusion - min07079.83 ± 10.7481.87 ± 15.8179.94 ± 14.49
Post Infusion - min08078.44 ± 10.9283.87 ± 11.5480.33 ± 16.22
Post Infusion - min09079.11 ± 12.3682.33 ± 12.8279.22 ± 17.16
Post Infusion - min10079.17 ± 12.6684.67 ± 12.5880.00 ± 16.95
Post Infusion - min11079.67 ± 11.7482.80 ± 13.6180.61 ± 16.55
Post Infusion - min12079.56 ± 11.9883.47 ± 13.4480.00 ± 16.37
Other pre-specifiedHeart Rate Per Infusion Phase by Group

Infusion 2 (Day 14) - Heart rate at all time points by group "Phase" in this analysis refers to the infusion stage as defined in the protocol.

Time frame:
Day 14 - Phase 1 - Baseline = min000s1 and @5 min; Phase 2 - Baseline = min000 then every 10 minutes for 4 hours; Post Infusion - Baseline = min000, then every 10 minutes for 2 hours
Reported as:
Mean · bpm
Heart Rate Per Infusion Phase by Group
bpmDrug-DrugPlacebo-DrugPlacebo - Placebo
Phase 1 - min000s177.38 ± 11.7775.08 ± 13.9476.94 ± 18.50
Phase 1 - min005s179.69 ± 12.4376.77 ± 14.8678.67 ± 17.85
Phase 2 - min00081.06 ± 11.2577.77 ± 15.2478.72 ± 17.75
Phase 2 - min00582.31 ± 12.8881.38 ± 15.3276.39 ± 17.77
Phase 2 - min01081.50 ± 13.4680.62 ± 16.4477.12 ± 17.19
Phase 2 - min01581.38 ± 12.9980.92 ± 15.4076.06 ± 17.11
Phase 2 - min02082.06 ± 12.1379.69 ± 16.7374.89 ± 16.97
Phase 2 - min02582.31 ± 12.3580.69 ± 18.0876.22 ± 16.81
Phase 2 - min03081.50 ± 10.2281.15 ± 16.3276.17 ± 15.73
Phase 2 - min04079.88 ± 13.6181.69 ± 15.5076.72 ± 15.35
Phase 2 - min05080.25 ± 12.2378.85 ± 15.4275.00 ± 16.30
Phase 2 - min06079.69 ± 15.1279.69 ± 14.6375.50 ± 15.75
Phase 2 - min07081.69 ± 13.8581.31 ± 13.5375.06 ± 16.28
Phase 2 - min08079.44 ± 13.9380.23 ± 14.1175.39 ± 14.61
Phase 2 - min09078.00 ± 14.5879.58 ± 14.7173.78 ± 15.56
Phase 2 - min10079.94 ± 14.2978.17 ± 14.6676.11 ± 15.15
Phase 2 - min11083.33 ± 11.5880.15 ± 15.5175.17 ± 15.52
Phase 2 - min12082.47 ± 12.9781.25 ± 16.1674.56 ± 14.27
Phase 2 - min13082.13 ± 13.0378.75 ± 15.2475.11 ± 13.60
Phase 2 - min14081.73 ± 13.9580.69 ± 14.9275.89 ± 15.87
Phase 2 - min15081.40 ± 12.5778.75 ± 13.5975.78 ± 14.53
Phase 2 - min16081.53 ± 13.2080.00 ± 11.2675.33 ± 13.75
Phase 2 - min17081.60 ± 14.4678.75 ± 12.5575.06 ± 14.43
Phase 2 - min18080.00 ± 12.9181.25 ± 12.8174.78 ± 14.10
Phase 2 - min19080.93 ± 12.9180.58 ± 16.3773.94 ± 14.18
Phase 2 - min20081.60 ± 14.3980.33 ± 14.2775.00 ± 12.63
Phase 2 - min21084.73 ± 11.9380.75 ± 17.1275.33 ± 15.04
Phase 2 - min22084.07 ± 12.5579.92 ± 13.9274.61 ± 14.46
Phase 2 - min23085.07 ± 11.7878.00 ± 14.5977.56 ± 14.61
Phase 2 - min24082.53 ± 13.7380.42 ± 12.5576.72 ± 15.69
Post Infusion - min00081.50 ± 13.8579.25 ± 14.7776.22 ± 16.13
Post Infusion - min00577.44 ± 12.1973.25 ± 13.9779.06 ± 16.00
Post Infusion - min01077.38 ± 13.6473.75 ± 13.6077.78 ± 15.38
Post Infusion - min01575.13 ± 13.5975.17 ± 12.7178.83 ± 14.50
Post Infusion - min02078.88 ± 13.7276.92 ± 11.2478.39 ± 14.74
Post Infusion - min02579.25 ± 12.4675.75 ± 14.1477.44 ± 12.87
Post Infusion - min03080.31 ± 11.1674.83 ± 11.7678.33 ± 13.92
Post Infusion - min04080.63 ± 16.6674.92 ± 10.4278.39 ± 13.85
Post Infusion - min05079.00 ± 11.8975.67 ± 12.2078.33 ± 14.58
Post Infusion - min06078.00 ± 11.3577.08 ± 13.2179.11 ± 13.64
Post Infusion - min07078.81 ± 11.1277.75 ± 13.9277.50 ± 13.95
Post Infusion - min08080.69 ± 10.8775.92 ± 14.8578.06 ± 14.94
Post Infusion - min09080.25 ± 10.0778.42 ± 16.5578.89 ± 14.29
Post Infusion - min10080.06 ± 10.5179.75 ± 16.8080.17 ± 14.29
Post Infusion - min11079.88 ± 10.2577.50 ± 16.9480.22 ± 14.72
Post Infusion - min12080.19 ± 11.7380.83 ± 17.0278.44 ± 14.30
Other pre-specifiedECG Measures at All Time Points by Group

Infusion 1 (Day 0) - ECG measures at all time points by group

Time frame:
Day 0 - Baseline (pre-infusion), During Infusion (@30 min), Post-Infusion (@60min)
Reported as:
Mean · mm/sec
ECG Measures at All Time Points by Group
mm/secDrug - DrugPlacebo - DrugPlacebo - Placebo
Baseline_PR Interval162.84 ± 30.09149.11 ± 11.52164.56 ± 19.61
Baseline_QRS Interval91.37 ± 11.3786.89 ± 8.7688.11 ± 10.12
Baseline_QT Interval380.16 ± 26.60384.28 ± 31.47381.94 ± 36.50
Baseline_RR Interval0.81 ± 0.190.82 ± 0.150.81 ± 0.19
30min_PR Interval159.63 ± 34.81152.40 ± 12.44167.59 ± 21.30
30min_QRS Interval89.79 ± 11.2288.00 ± 10.3989.12 ± 9.97
30min_QT Interval385.11 ± 25.55385.27 ± 29.72385.53 ± 42.92
30min_RR Interval0.76 ± 0.120.81 ± 0.160.81 ± 0.20
End_PR Interval165.94 ± 38.63149.43 ± 11.33165.63 ± 25.23
End_QRS Interval91.67 ± 13.4387.50 ± 9.6389.00 ± 10.09
End_QT Interval371.94 ± 41.97377.00 ± 25.33391.13 ± 43.35
End_RR Interval0.79 ± 0.120.80 ± 0.110.82 ± 0.20
Other pre-specifiedECG Measures at All Time Points by Group

Infusion 2 (Day 14) - ECG measures at all time points by group

Time frame:
Day 14 - Baseline (pre-infusion), During Infusion (@30 min), Post-Infusion (@60min)
Reported as:
Mean · mm/sec
ECG Measures at All Time Points by Group
mm/secDrug - DrugPlacebo - DrugPlacebo - Placebo
Baseline_PR Interval155.47 ± 23.46149.46 ± 15.61167.61 ± 20.02
Baseline_QRS Interval92.82 ± 11.2986.46 ± 10.0591.33 ± 12.45
Baseline_QT Interval379.35 ± 29.59385.69 ± 35.84387.33 ± 38.27
Baseline_RR Interval0.80 ± 0.170.86 ± 0.160.84 ± 0.19
30min_PR Interval156.18 ± 21.95146.69 ± 14.85172.00 ± 19.76
30min_QRS Interval90.18 ± 11.9587.00 ± 7.9888.44 ± 10.76
30min_QT Interval389.18 ± 25.33360.08 ± 46.52380.44 ± 33.30
30min_RR Interval0.75 ± 0.110.77 ± 0.180.82 ± 0.18
End_PR Interval160.41 ± 26.48153.55 ± 19.87165.63 ± 21.08
End_QRS Interval95.41 ± 9.9086.64 ± 9.9089.50 ± 9.97
End_QT Interval387.06 ± 38.89384.91 ± 29.89383.25 ± 31.60
End_RR Interval0.80 ± 0.160.86 ± 0.110.81 ± 0.16
Other pre-specifiedIncidence of Treatment-Emergent Adverse Events (TEAEs)

Incidence of Treatment-Emergent Adverse Events (TEAE) by Treatment Group. A treatment emergent adverse event (TEAE) is an AE that either began following initiation of study treatment or was present prior to the initiation of the treatment, but increased in frequency or severity following initiation treatment, regardless of causality.

Time frame:
The period of observation for collection of treatment-emergent adverse events extends from Day 0 treatment through the final visit at Day 28.
Reported as:
Number · # of TEAEs
Incidence of Treatment-Emergent Adverse Events (TEAEs)
# of TEAEsDrug - DrugPlacebo - DrugPlacebo - Placebo
Incidence of Treatment-Emergent Adverse Events (TEAEs)13810
Other pre-specifiedNumber of Subject Withdrawals Due to Treatment-Emergent Adverse Events (TEAEs)

Incidence of Treatment-Emergent Adverse Events (TEAE) by Treatment Group. A treatment emergent adverse event (TEAE) is an AE that either began following initiation of study treatment or was present prior to the initiation of the treatment, but increased in frequency or severity following initiation treatment, regardless of causality.

Time frame:
The period of observation extends from Day 0 treatment through the final visit at Day 28
Reported as:
Number · participants
Number of Subject Withdrawals Due to Treatment-Emergent Adverse Events (TEAEs)
participantsDrug - DrugPlacebo - DrugPlacebo - Placebo
Number of Subject Withdrawals Due to Treatment-Emergent Adverse Events (TEAEs)340
Other pre-specifiedSystematic Assessment for Treatment Emergent Effects-Systematic Inquiry (SAFTEE-SI) - Percent of Participants Reporting Experiencing Symptoms at "Moderate" or "Severe" Level for the 10 Most Frequently Reported Symptoms Post Randomization

The Systematic Assessment for Treatment Emergent Effects-Systematic Inquiry (SAFTEE-SI): This is a self-rated 77-item questionnaire organized into 13 body areas assessing possible adverse events during the course of the trial.

Time frame:
Baseline (Day - 1), Follow-Up = reported at any assessment thereafter, including 7 hours after Infusions #1 and #2, Baseline 2 (Day 13) and final follow-up, including early termination visits.
Reported as:
Number · percentage of participants
Systematic Assessment for Treatment Emergent Effects-Systematic Inquiry (SAFTEE-SI) - Percent of Participants Reporting Experiencing Symptoms at "Moderate" or "Severe" Level for the 10 Most Frequently Reported Symptoms Post Randomization
percentage of participantsDrug - DrugPlacebo - DrugPlacebo - Placebo
10. Baseline - Hearing or seeing things22.225.022.2
10. Follow-Up - Hearing or seeing things33.331.316.7
3. Baseline - Feeling drowsy or sleepy16.70.022.2
3. Follow-Up - Feeling drowsy or sleepy22.225.022.2
8. Baseline - Trouble concentrating16.76.322.2
8. Follow-Up - Trouble concentrating11.118.827.8
7. Baseline - Poor memory11.16.327.8
7. Follow-Up - Poor memory5.625.022.2
1. Baseline - Trouble Sleeping16.76.327.8
1. Follow-Up - Trouble Sleeping11.112.522.2
4. Baseline - Feeling nervous or hyper5.618.833.3
4. Follow-Up - Feeling nervous or hyper5.618.822.2
18. Baseline - Dry mouth5.612.511.1
18. Follow-Up - Dry mouth5.625.016.7
34. Baseline - Frequent need to urinate0.06.311.1
34. Follow-Up - Frequent need to urinate5.618.816.7
17. Baseline - Stuffy nose5.66.316.7
17. Follow-Up - Stuffy nose5.618.811.1
52. Baseline - Hot flashes0.06.35.6
52. Follow-Up - Hot flashes11.16.316.7

Adverse events

Collected over The period of observation for collection of adverse events extends from the time the subject gave informed consent until the final visit at Day 28.. Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Drug - Drug0/23 (0%)0/23 (0%)11/23 (47.8%)
Placebo - Drug0/19 (0%)0/19 (0%)9/19 (47.4%)
Placebo - Placebo0/18 (0%)0/18 (0%)9/18 (50%)
Most frequent other events
Showing 10 of 33
Most frequent other events
EventDrug - DrugPlacebo - DrugPlacebo - Placebo
HypotensionCardiac disorders5/231/191/18
NauseaGastrointestinal disorders0/233/192/18
HeadacheNervous system disorders3/232/190/18
Chest PainCardiac disorders0/231/192/18
PalpitationsCardiac disorders0/230/192/18
Low O2 Saturation RateRespiratory, thoracic and mediastinal disorders1/232/190/18
Nausea/VomitingGastrointestinal disorders0/232/190/18
RashSkin and subcutaneous tissue disorders2/231/190/18
FlushingVascular disorders2/230/190/18
Decreased LibidoReproductive system and breast disorders1/230/191/18

Baseline characteristics

Age, Continuous
Age, Continuous(years)Drug - DrugPlacebo - DrugPlacebo - PlaceboTotal
Mean47.1 ± 10.545.9 ± 12.340.4 ± 11.044.5 ± 11.3
Sex: Female, Male
Sex: Female, Male(Participants)Drug - DrugPlacebo - DrugPlacebo - PlaceboTotal
Female44412
Male14121440
Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)Drug - DrugPlacebo - DrugPlacebo - PlaceboTotal
Hispanic or Latino1124
Not Hispanic or Latino17151648
Unknown or Not Reported0000
Race/Ethnicity, Customized
Race/Ethnicity, Customized(Participants)Drug - DrugPlacebo - DrugPlacebo - PlaceboTotal
White109625
Black651122
Asian1214
Other1001
Region of Enrollment
Region of Enrollment(Participants)Drug - DrugPlacebo - DrugPlacebo - PlaceboTotal
United States18161852
The Positive and Negative Syndrome Scale (PANSS) at Baseline (Day 3)
The Positive and Negative Syndrome Scale (PANSS) at Baseline (Day 3)(units on a scale)Drug - DrugPlacebo - DrugPlacebo - PlaceboTotal
PANSS -total83.6 ± 10.077.6 ± 8.881.7 ± 8.880.9 ± 9.2
PANSS - positive24.9 ± 3.522.3 ± 3.422.6 ± 3.123.26 ± 3.3
PANSS - negative20.9 ± 5.520.3 ± 5.021.4 ± 4.620.8 ± 15.1
08

Study locations

4 sites
  • Schizophrenia Clinical Research Program, Massachusetts General Hospital
    Boston, Massachusetts 02114, United States
  • University of Massachusetts Medical School
    Worcester, Massachusetts 01605, United States
  • Zucker Hillside Hospital
    Glen Oaks, New York 11004, United States
  • New York University Langone Medical Center/Bellevue Hospital
    New York, New York 10016, United States
09

References and documents

Publications

  • Brown HE, Freudenreich O, Fan X, Heard SO, Goff D, Petrides G, Harrington AL, Kane JM, Judge H, Hoeppner B, Fava M, Perlis RH. Efficacy and Tolerability of Adjunctive Intravenous Sodium Nitroprusside Treatment for Outpatients With Schizophrenia: A Randomized Clinical Trial. JAMA Psychiatry. 2019 Jul 1;76(7):691-699. doi: 10.1001/jamapsychiatry.2019.0151. PubMed 30916714 ↗

Study documents

  • Study protocol · Dec 1, 2016
  • Statistical analysis plan · Dec 1, 2016

Documents are hosted by the registry — open the source record to download them.

10

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Oct 2, 2018, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT02164981
Lead sponsor
Massachusetts General Hospital
Collaborators
Stanley Medical Research Institute
Responsible party
Maurizio Fava, MD (Director, Clinical Research Program, Massachusetts General Hospital) — Principal investigator
First posted
Jun 17, 2014
Start date
May 1, 2015
Primary completion
Mar 31, 2017
Completion
Apr 5, 2017
Results posted
Oct 2, 2018
Last update
Oct 2, 2018

Study contacts

Maurizio Fava, MD
principal investigator · Massachusetts General Hospital
Roy Perlis, MD MSc
principal investigator · Massachusetts General Hospital

Oversight

Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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