A Multiple Dose Study of Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of ABT-288 in Stable Subjects With Schizophrenia

Evaluate the safety, tolerability and pharmacokinetics of ABT-288 in order to determine the maximum tolerated dose of ABT-288 in stable schizophrenic volunteers receiving treatment with an atypical antipsychotic.

Study Overview

• Status: Completed
• Conditions: Schizophrenia
• Intervention / Treatment: Drug: Placebo; Drug: ABT-288

• Study Type: Interventional
• Enrollment (Actual): 81
• Phase: Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Subject has signed informed consent;
• Current DSM-IV-TR diagnosis of schizophrenia;
• Clinically stable on the same single second-generation antipsychotic for the past 8 weeks;
• Meets study-specific PANSS criteria;
• Willing and able to cooperate with cognitive testing
• Females are not pregnant, not breast-feeding;
• Females are post-menopausal or surgically sterile or practicing birth control;
• Males are surgically sterile or agree to be sexually inactive or use barrier method of birth control

Exclusion Criteria:

• Subject has a substance dependence disorder that has not been in sustained remission for at least 1 year;
• Diagnosis of schizoaffective disorder;
• Bipolar disorder, manic episode, dementia, OCD, or drug-induced psychosis or current major depressive disorder;
• Diagnoses with mental retardation; acute psychosis hospitalization within past 6 months;
• Current clozapine treatment; suicidal ideation or behavior;
• BMI of 39 or greater; current homicidal or violent ideation;
• Medical or CNS condition other than schizophrenia that could affect cognitive performance or testing; relevant drug sensitivity or allergy; positive urine screen for alcohol or drugs of abuse;
• Positive hepatitis or HIV test result;
• Recent clinically significant illness/infection or surgery;
• Recent blood product transfusion, donation or loss of 5 mL/kg of blood;
• Visual, hearing or communication disability

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Single Group Assignment
• Masking: Double

Number of Arms

9

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1; ABT-288 vs placebo capsules administered orally once daily for 14 days	Drug: Placebo; See Arm Description for details.; Drug: ABT-288; See Arm Description for details.
Experimental: 2; ABT-288 vs placebo capsules administered orally once daily for 14 days	Drug: Placebo; See Arm Description for details.; Drug: ABT-288; See Arm Description for details.
Experimental: 3; ABT-288 vs placebo capsules administered orally once daily for 14 days	Drug: Placebo; See Arm Description for details.; Drug: ABT-288; See Arm Description for details.
Experimental: 4; ABT288 vs placebo administered orally once daily for 14 days	Drug: Placebo; See Arm Description for details.; Drug: ABT-288; See Arm Description for details.
Experimental: 5; ABT-288 vs placebo administered orally once daily for 14 days	Drug: Placebo; See Arm Description for details.; Drug: ABT-288; See Arm Description for details.
Experimental: 6; ABT-288 vs placebo administered orally once daily for 14 days	Drug: Placebo; See Arm Description for details.; Drug: ABT-288; See Arm Description for details.
Experimental: 7; ABT-288 vs placebo administered orally once daily for 14 days	Drug: Placebo; See Arm Description for details.; Drug: ABT-288; See Arm Description for details.
Experimental: 8; ABT-288 vs placebo administered orally once daily for 14 days	Drug: Placebo; See Arm Description for details.; Drug: ABT-288; See Arm Description for details.
Experimental: 9; ABT-288 vs placebo administered orally once daily for 14 days	Drug: Placebo; See Arm Description for details.; Drug: ABT-288; See Arm Description for details.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Physical Exams, Brief Neurological Exams, Vitals, Orthostatic Vitals, ECG, Laboratory tests,	Days -1 to 21
Pharmacokinetics; optional CSF for arms 7, 8 & 9	Days -1 to 21

Secondary Outcome Measures

Outcome Measure	Time Frame
Extrapyramidal Symptom Rating Scale	Day -1, Day 14
Columbia Suicide Severity Rating Scale	Screening, Day 15
Pharmacodynamics: CANTAB & PANSS	Screening, Day -1, Day 14
Pharmacodynamics: Pittsburgh Sleep Quality Index-Modified	Day -1, Day 15

Collaborators and Investigators

• Sponsor: AbbVie

Publications and helpful links

General Publications

• Othman AA, Haig G, Florian H, Locke C, Gertsik L, Dutta S. The H3 antagonist ABT-288 is tolerated at significantly higher exposures in subjects with schizophrenia than in healthy volunteers. Br J Clin Pharmacol. 2014 Jun;77(6):965-74. doi: 10.1111/bcp.12281.

Study record dates

Study Major Dates

• Study Start: November 1, 2008
• Primary Completion (Actual): December 1, 2009

Study Registration Dates

• First Submitted: April 27, 2009
• First Submitted That Met QC Criteria: April 27, 2009
• First Posted (Estimate): April 28, 2009

Study Record Updates

• Last Update Posted (Actual): November 21, 2017
• Last Update Submitted That Met QC Criteria: November 17, 2017
• Last Verified: October 1, 2010

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Schizophrenia Spectrum and Other Psychotic Disorders; Schizophrenia
• Other Study ID Numbers: M10-752