NCT02075047

Efficacy and Safety Trial of Flexible Doses of Oral Ziprasidone in Children and Adolescents With Bipolar I Disorder

Terminated Phase 3 Results posted Last updated 16 June 2021

What this trial tests

Phase 3 trial testing placebo oral capsules in Bipolar Disorder in 171 participants. Terminated before completion.

Timeline

23 May 2014

Primary endpoint
11 April 2020

18 May 2020

Quick facts

Lead sponsor	Pfizer's Upjohn has merged with Mylan to form Viatris Inc.
Phase	Phase 3
Status	Terminated
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	triple
Primary purpose	treatment
Enrollment	171
Start date	23 May 2014
Primary completion	11 April 2020
Estimated completion	18 May 2020
Sites	50 locations across United States, Ukraine

Drugs / interventions tested

• placebo oral capsules
• ziprasidone oral capsules — full drug profile →

Conditions studied

• Bipolar Disorder — all drugs for Bipolar Disorder →

Sponsor

Pfizer's Upjohn has merged with Mylan to form Viatris Inc. — full company profile →

Who can join

Adults 10 to 17, any sex, with Bipolar Disorder. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Change From Baseline in Young Mania Rating Scale (YMRS) Total Score at Week 4 Primary · Baseline, Week 4

YMRS: an 11-item scale that measured the severity of manic episodes. Four items (irritability, speech, thought content, and disruptive/ aggressive behavior) were rated on a scale from 0 (symptom absent) to 8 (symptom extremely severe). The remaining items were rated on a scale from 0 (symptom absent) to 4 (symptom extremely severe). YMRS total score was sum of score of all 11 items and ranged from 0 (no symptoms) to 60 (extreme severity of symptoms), higher score indicated higher severity of mania.

Group	Value	95% CI
Ziprasidone	-16.51	± 1.15
Placebo	-12.29	± 1.10

Change From Baseline in Clinical Global Impression of Severity (CGI-S) Score at Weeks 1, 2, 3, and 4 Secondary · Baseline, Week 1, 2, 3, 4

CGI-S: 7-point clinician rated scale to assess severity of participant's current illness state; range: 1 (normal - not ill at all) to 7 (among the most extremely ill), higher scores indicated more severity of illness.

Change at Week 1

Group	Value	95% CI
Ziprasidone	-0.91	± 0.10
Placebo	-0.47	± 0.10

Change at Week 2

Group	Value	95% CI
Ziprasidone	-1.13	± 0.12
Placebo	-0.91	± 0.12

Change at Week 3

Group	Value	95% CI
Ziprasidone	-1.53	± 0.13
Placebo	-1.14	± 0.13

Change at Week 4

Group	Value	95% CI
Ziprasidone	-1.59	± 0.14
Placebo	-1.32	± 0.14

Change From Baseline in the Young Mania Rating Scale (YMRS) Total Score at Weeks 1, 2, and 3 Secondary · Baseline, Week 1, 2, 3

YMRS: an 11-item scale that measured the severity of manic episodes. Four items (irritability, speech, thought content, and disruptive/ aggressive behavior) were rated on a scale from 0 (symptom absent) to 8 (symptom extremely severe). The remaining items were rated on a scale from 0 (symptom absent) to 4 (symptom extremely severe). YMRS total score was sum of score of all 11 items and ranged from 0 (no symptoms) to 60 (extreme severity of symptoms), higher score indicated higher severity of mania.

Change at Week 1

Group	Value	95% CI
Ziprasidone	-11.43	± 0.94
Placebo	-5.58	± 0.93

Change at Week 2

Group	Value	95% CI
Ziprasidone	-13.70	± 1.02
Placebo	-9.53	± 1.01

Change at Week 3

Group	Value	95% CI
Ziprasidone	-16.79	± 1.04
Placebo	-11.17	± 1.01

Clinical Global Impression of Improvement (CGI-I) Scores at Weeks 1, 2, 3, and 4 Secondary · Baseline, Week 1, 2, 3, 4

CGI-I: 7-point clinician rated scale which rates the participant's improvement or worsening from baseline, ranging from 1 (very much improved) to 7 (very much worse), higher scores indicate less improvement.

Change at Week 1

Group	Value	95% CI
Ziprasidone	2.89	± 0.11
Placebo	3.41	± 0.11

Change at Week 2

Group	Value	95% CI
Ziprasidone	2.75	± 0.12
Placebo	2.89	± 0.12

Change at Week 3

Group	Value	95% CI
Ziprasidone	2.42	± 0.12
Placebo	2.68	± 0.12

Change at Week 4

Group	Value	95% CI
Ziprasidone	2.30	± 0.13
Placebo	2.64	± 0.13

Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) Secondary · Screening (2 Weeks prior to Day 1) up to maximum of 5 Weeks after administration of the final dose of study medication (maximum up to 11 weeks)

An AE was any untoward medical occurrence in a participant who received study medication without regard to possibility of causal relationship to it. SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/ incapacity; congenital anomaly. AEs included both serious and all non-serious AEs.

AEs

Group	Value	95% CI
Ziprasidone	67
Placebo	50

SAEs

Group	Value	95% CI
Ziprasidone	3
Placebo	0

Number of Participants With Columbia Classification Algorithm of Suicide Assessment (C-CASA) Categorization Mapped From Columbia-Suicide Severity Rating Scale (C-SSRS) Secondary · Screening (2 Weeks prior to Day 1), Baseline (Day 1), Week 1, 2, 3, 4, Early Termination Visit (anytime from Day 1 to Week 4), Follow up Visit (anytime from Day 1 up to 5 weeks after last dose of study drug = anytime from Day 1 to Week 9)

C-SSRS: a measure used to identify and assess participants at risk for suicide. It is a semi-structured interview that captures the occurrence, severity, and frequency of suicide-related thoughts and behaviors. C-SSRS items were mapped to the following C-CASA categories: completed suicide, attempted suicide (actual attempt; aborted attempt; interrupted attempt), non-suicidal self-injurious behavior, preparatory acts, suicidal ideation (wish to be dead; non-specific active suicidal thoughts; active suicidal ideation with any methods \[not plan\], without intent to act; active suicidal ideation

Screening: Actual Attempt

Group	Value	95% CI
Ziprasidone	5
Placebo	3

Screening: Interrupted Attempt

Group	Value	95% CI
Ziprasidone	0
Placebo	1

Screening: Non-Suicidal Self-Injurious Behavior

Group	Value	95% CI
Ziprasidone	10
Placebo	5

Screening: Preparatory Acts

Group	Value	95% CI
Ziprasidone	0
Placebo	1

Screening: Wish To Be Dead

Group	Value	95% CI
Ziprasidone	25
Placebo	25

Screening: Non-specific Active Suicidal Thoughts

Group	Value	95% CI
Ziprasidone	16
Placebo	13

Baseline: Wish To Be Dead

Group	Value	95% CI
Ziprasidone	1
Placebo	0

Baseline: Active Suicidal Thoughts With No Plan, Intent

Group	Value	95% CI
Ziprasidone	4
Placebo	7

Number of Participants Who Took at Least 1 Concomitant Medication and Concomitant Non-Drug Treatments/Procedures Secondary · Screening (2 Weeks prior to Day 1) up to 1 Week after administration of the final dose of study medication (maximum for 7 Weeks)

Concomitant medications or treatments were those prescription and over-the-counter drugs and supplements or non drug treatment/procedures other than the study medication.

Concomitant Medication

Group	Value	95% CI
Ziprasidone	55
Placebo	47

Concomitant Non-Drug Treatments/Procedures

Group	Value	95% CI
Ziprasidone	6
Placebo	7

Number of Participants With Laboratory Abnormalities Secondary · Screening (2 Weeks prior to Day 1) up to 1 Week after administration of the final dose of study medication (maximum for 7 Weeks)

Criteria: Hematology-hemoglobin(Hg),hematocrit,erythrocytes(ery)\<0.8\*LLN,ery mean corpuscular volume \<0.9\*LLN\>1.1\*ULN,platelets\<0.5\*LLN\>1.75\*ULN,leukocytes(leu)\<0.6\*LLN\>1.5\*ULN,lymphocytes(lym),lym/leu,neutrophils(neu),neu/leu\<0.8\*LLN\>1.2\*ULN,basophils (bas),bas/leu, eosinophils(eos), eos/leu, monocytes(mon),mon/leu\>1.2\*ULN; Clinical chemistry bilirubin: total, direct, indirect\>1.5\*ULN, aspartate aminotransferase,alanine aminotransferase, gamma glutamyl transferase, lactate dehydrogenase,alkaline phosphatase\>3.0\*ULN,protein,albumin\<0.8\*LLN\>1.2\*ULN,blood urea nitroge

Group	Value	95% CI
Ziprasidone	50
Placebo	62

Number of Participants With Physical Examination Abnormalities Secondary · Screening (2 Weeks prior to Day 1) up to Week 4

Parameters assessed for physical examination included: oral/tympanic temperature, general appearance, skin, head, ears, eyes, nose, throat, heart, lungs, breasts (if medically indicated), abdomen, external genitalia \[if medically indicated\], extremities, back/spinal system, lymph nodes or worsening of medical history conditions. Abnormality in physical examination was at the investigator's discretion.

Group	Value	95% CI
Ziprasidone	4
Placebo	5

Change From Baseline in Blood Pressure at Week 1, 2, 3, 4, Early Termination Visit and Follow-up Visit Secondary · Baseline, Week 1, 2, 3, 4, Early Termination Visit (anytime from Day 1 to Week 4), Follow up Visit (anytime from Day 1 up to 5 weeks after last dose of study drug = anytime from Day 1 to Week 9)

Change from baseline in sitting and standing systolic blood pressure and diastolic blood pressure in millimeter of mercury (mmHg) was reported.

Sitting Systolic Blood Pressure, Baseline

Group	Value	95% CI
Ziprasidone	110.5	± 9.84
Placebo	110.9	± 11.45

Sitting Systolic Blood Pressure, Change at Week 1

Group	Value	95% CI
Ziprasidone	0.7	± 6.90
Placebo	0.2	± 8.71

Sitting Systolic Blood Pressure, Change at Week 2

Group	Value	95% CI
Ziprasidone	0.2	± 9.65
Placebo	0.1	± 9.26

Sitting Systolic Blood Pressure, Change at Week 3

Group	Value	95% CI
Ziprasidone	-0.7	± 10.12
Placebo	-0.6	± 8.93

Sitting Systolic Blood Pressure, Change at Week 4

Group	Value	95% CI
Ziprasidone	-0.7	± 10.60
Placebo	-2.2	± 10.39

Sitting Systolic Blood Pressure, Change at Early Termination

Group	Value	95% CI
Ziprasidone	0.7	± 7.87
Placebo	6.4	± 5.90

Sitting Systolic Blood Pressure, Change at Follow up

Group	Value	95% CI
Ziprasidone	-1.4	± 12.44
Placebo	-2.2	± 8.35

Standing Systolic Blood Pressure, Baseline

Group	Value	95% CI
Ziprasidone	110.7	± 9.53
Placebo	112.0	± 10.16

Change From Baseline in Pulse Rate at Week 1, 2, 3, 4, Early Termination Visit and Follow-up Visit Secondary · Baseline, Week 1, 2, 3, 4, Early Termination Visit (anytime from Day 1 to Week 4), Follow up Visit (anytime from Day 1 up to 5 weeks after last dose of study drug = anytime from Day 1 to Week 9)

Change from baseline pulse rate in (beats per minute) was reported in sitting and standing positions.

Sitting, Baseline

Group	Value	95% CI
Ziprasidone	79.1	± 12.58
Placebo	75.8	± 9.80

Sitting, Change at Week 1

Group	Value	95% CI
Ziprasidone	-0.9	± 11.24
Placebo	-2.0	± 9.40

Sitting, Change at Week 2

Group	Value	95% CI
Ziprasidone	-2.4	± 11.75
Placebo	1.5	± 8.82

Sitting, Change at Week 3

Group	Value	95% CI
Ziprasidone	-0.5	± 12.79
Placebo	2.3	± 10.61

Sitting, Change at Week 4

Group	Value	95% CI
Ziprasidone	-2.3	± 11.49
Placebo	-0.2	± 10.30

Early Termination: Sitting

Group	Value	95% CI
Ziprasidone	3.5	± 14.02
Placebo	1.6	± 7.02

Follow up: Sitting

Group	Value	95% CI
Ziprasidone	2.0	± 11.32
Placebo	3.1	± 11.73

Standing, Baseline

Group	Value	95% CI
Ziprasidone	84.6	± 12.23
Placebo	83.3	± 10.95

Change From Baseline in Height and Waist Circumference at Week 4 and Early Termination Visit Secondary · Baseline, Week 4, Early Termination Visit (anytime from Day 1 to Week 4)

Change from baseline in height and waist circumference in centimeter (cm) was reported.

Height, Baseline

Group	Value	95% CI
Ziprasidone	157.9	± 10.63
Placebo	159.7	± 11.41

Height, Change at Week 4

Group	Value	95% CI
Ziprasidone	0.4	± 0.60
Placebo	0.7	± 1.77

Height, Change at Early Termination

Group	Value	95% CI
Ziprasidone	0.2	± 0.54
Placebo	0.5	± 0.73

Waist Circumference, Baseline

Group	Value	95% CI
Ziprasidone	76.9	± 12.22
Placebo	74.9	± 10.56

Waist Circumference, Change at Week 4

Group	Value	95% CI
Ziprasidone	-0.1	± 2.79
Placebo	0.3	± 3.26

Waist Circumference, Change at Early Termination

Group	Value	95% CI
Ziprasidone	0.4	± 3.77
Placebo	1.0	± 1.74

Adverse events — posted to ClinicalTrials.gov

Time frame: Screening (2 Weeks prior to Day 1) up to maximum of 5 Weeks after administration of the final dose of study medication (maximum up to 11 weeks). Reporting threshold: 2%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Ziprasidone

Serious: 3/86 (3%)

Deaths: 0/86

Placebo

Serious: 0/85 (0%)

Deaths: 0/85

Serious adverse events (5 terms)

Reaction	System	Ziprasidone	Placebo
Chest pain	General disorders	—	—
Sunburn	Injury, poisoning and procedural complications	—	—
Anxiety	Psychiatric disorders	—	—
Suicidal ideation	Psychiatric disorders	—	—
Suicide attempt	Psychiatric disorders	—	—

Other adverse events (26 terms — click to expand)

Reaction	System	Ziprasidone	Placebo
Somnolence	Nervous system disorders	—	—
Fatigue	General disorders	—	—
Nausea	Gastrointestinal disorders	—	—
Decreased appetite	Metabolism and nutrition disorders	—	—
Vomiting	Gastrointestinal disorders	—	—
Headache	Nervous system disorders	—	—
Sedation	Nervous system disorders	—	—
Dizziness	Nervous system disorders	—	—
Akathisia	Nervous system disorders	—	—
Agitation	Psychiatric disorders	—	—
Abdominal pain upper	Gastrointestinal disorders	—	—
Upper respiratory tract infection	Infections and infestations	—	—
Increased appetite	Metabolism and nutrition disorders	—	—
Anxiety	Psychiatric disorders	—	—
Insomnia	Psychiatric disorders	—	—
Diarrhoea	Gastrointestinal disorders	—	—
Salivary hypersecretion	Gastrointestinal disorders	—	—
Joint stiffness	Musculoskeletal and connective tissue disorders	—	—
Musculoskeletal stiffness	Musculoskeletal and connective tissue disorders	—	—
Myalgia	Musculoskeletal and connective tissue disorders	—	—
Hypersomnia	Nervous system disorders	—	—
Speech disorder	Nervous system disorders	—	—
Tremor	Nervous system disorders	—	—
Initial insomnia	Psychiatric disorders	—	—
Irritability	Psychiatric disorders	—	—
Rash	Skin and subcutaneous tissue disorders	—	—

Most-reported serious reactions: Chest pain, Sunburn, Anxiety, Suicidal ideation, Suicide attempt.

Data from ClinicalTrials.gov NCT02075047 adverse events section.

Sponsor's own description

The purpose of this study is to determine if ziprasidone is safe and effective for the treatment of children and adolescents (ages 10-17) with bipolar I disorder (manic or mixed).

Publications & conference data

1 peer-reviewed publication reference this trial (live from Europe PMC):

1. Efficacy, Safety, and Tolerability of Flexibly Dosed Ziprasidone in Children and Adolescents with Mania in Bipolar I Disorder: A Randomized Placebo-Controlled Replication Study.
   Findling RL, Atkinson S, Bachinsky M, Raiter Y, et al · · 2022 · cited 4× · PMID 35394365 · DOI 10.1089/cap.2021.0121