SchizophreniaPhase 1NCT01346163
Add On Treatment for Cognitive Deficits in Schizophrenia
A Phase 1 study testing PF 03654746 in people with Schizophrenia, run by University of Pennsylvania at 1 site in United States.
Trial summary
This study will look at the impact of dosing as well as ongoing treatment with an investigation medication identified as PF-03654746, on cognitive and physiologic indicators of brain function. Read more about this study
- Who is it for?
- Ages 18 to 40 years
- Conditions the study is for
- Schizophrenia
- What is being tested?
- PF 03654746
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 16 participants
- Where
- 1 siteUnited States
- Study dates
- Apr 2009to Nov 2010
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 40 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- Initial Inclusion Criteria:
- Subjects must be competent to provide informed consent to participate in a clinical trial before any trial-related procedures can take place;
- Subjects must be willing and able to comply with scheduled visits, treatments, laboratory tests and other testing and study procedures;
- Subjects who participate must be willing to remain in-patient for at least one week at the beginning of each treatment period and remain in the hospital until judged by the Investigator to be clinically stable and able to be discharged to outpatient status;
- Subjects must be fluent in English and able to understand all study related materials;
- Subjects must be between the ages of 18-40 (inclusive) and if Female be of non-childbearing potential;
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- Body Mass Index (BMI) 18 to 40 kg/m2 and a total body weight of at least 50 kg (110 lbs);
- Psychiatric Inclusion Criteria:
- Subjects must have a current DSM-IV-TR diagnosis of schizophrenia of Paranoid (295.30), Disorganized (295.10), Undifferentiated (295.90) or Residual Type (295.60);
- Subjects must be receiving ongoing maintenance antipsychotic monotherapy with risperidone, olanzapine, quetiapine, ziprasidone, paliperidone or aripiprazole;
- Subjects must be on a stable medication treatment regimen 2 months, including concomitant psychotropic medications;
- Evidence of stable control of symptoms for 3 months (eg, no hospitalizations for schizophrenia, no increase in level of psychiatric care due to worsening of symptoms of schizophrenia);
- No more than moderate severity rating (4) on any individual PANSS positive symptom item (P1, P3, P5, P6) or formal thought disorder (P2), with no more than two moderate items in total;
- Calgary Depression Scale Score less than or equal to 10;
- Subjects must have a minimal level of extrapyramidal symptoms as documented by a score on the ESRS-A Global Parkinsonism scale of 3;
- Subjects must have an illness duration (from the time of diagnosis) of at least 1 year;
- Subjects will meet the following cognitive performance criteria:
- Performance less than the maximum cutoff (in parentheses) for at least ONE of the following MCCB tests: (i.) Letter-number span (20); (ii.) Hopkins Verbal Learning Test (HVLT) total (31); and (iii.) Continuous Performance T- test (CPT) d-prime (3.47);
- Able to complete the Baseline MCCB validly as assessed by a certified MCCB test administrator;
- Standard score greater than or equal to 75 on the National Adult Reading Test (NART) or other IQ measure.
Who cannot join
- Female subjects who still have child bearing potential and females who are breastfeeding;
- History of febrile illness within 5 days prior to the first dose;
- Any condition possibly affecting drug absorption (eg, gastrectomy);
- Subjects who have a positive urine drug screen which cannot be explained by prescribed medications;
- History of regular alcohol consumption exceeding 7 drinks/week for females or 14 drinks/week for men (1 drink = 5 ounces (150 mL) of wine or 12 ounces (360 mL) of beer or 1.5 ounces (45 mL) of hard liquor) within 6 months of screening;
- Treatment with an investigational drug within 30 days or 5 half-lives preceding the first dose of study medication;
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- 12-lead ECG demonstrating QTc less than or equal to 450 msec at screening;
- Subjects who are using disallowed concomitant medications and who will not be able to discontinue these concomitant medications prior to randomization;
- Subjects who have taken hormone replacement therapy within 28 days or have taken an herbal remedy 7 days prior to the first dose of trial medication;
- Subjects with other conditions that may increase the risk associated with trial participation or investigational product administration or may interfere with the interpretation of trial results, and in the judgment of the Investigator, would make the subject inappropriate for entry into this trial;
- Subjects with serologic evidence of acute hepatitis or chronic hepatitis and subjects with known hepatitis C antibodies and elevated LFTs;
- Subjects with AST and/or ALT 1.5xULN at the Screening Visit;
- Subjects with a current DSM-IV axis I diagnosis other than schizophrenia;
- Subjects with a concurrent psychiatric disorder other than schizophrenia coded on Axis I;
- Subjects who have previously participated in a trial using PF-03654746;
- Subjects who have DSM-IV defined psychoactive substance dependence (excluding nicotine dependence) within 12 months of screening or substance abuse within 3 months prior to Screening;
- Subjects currently using illicit psychoactive substances as evidenced by positive urine toxicology screen (utox positive for cannabinoids will not be exclusionary due to the long elimination half life of these substances);
- Subjects with evidence or history of mental retardation;
- Subjects with significant risk of suicidal or violent behavior;
- Subjects with a history of poor compliance;
- Subjects who have received clozapine or monoamine oxidase inhibitors in the month prior to randomization;
- Current treatment with haloperidol or other typical antipsychotic;
- Current treatment (within 4 weeks) with psychotropic agents known to act at the GABA-A receptor, including benzodiazepines; sedative-hypnotics other than trazodone and chloral hydrate; carbamazepine, gabapentin, lamotrigine, and valproic acid;
- Current treatment (within 4 weeks) with psychotropic agents known to effect cognition: amphetamine; barbiturates; lithium; MAOIs; methylphenidate;
- Current treatment (within 4 weeks) with herbal preparations with possible psychotropic effects (eg, St. Johns wort, kava-kava, Valerian, S-Adenosyl Methionine [SAMe]);
- Subjects with a history of seizures and or/seizure disorder, significant head injury/trauma, as defined by one or more of the following:
- Loss of consciousness (LOC) for more than 1 hour;
- Recurring seizures resulting from the head injury;
- Clear cognitive sequelae of the injury;
- Cognitive rehabilitation following the injury.
- Subjects with a history of clinically significant neurological, metabolic, hepatic, renal, hematological, pulmonary, cardiovascular, gastrointestinal, and/or urological disorders (eg, unstable angina, decompensated congestive heart failure, CNS infection or history of HIV seropositivity), which would pose a risk to the patient if they were to participate in the study or that might confound the results of the study. Active medical conditions that are minor or well controlled are not exclusionary if they do not affect risk to the patient or the study results. For example, the following are not exclusionary: a) stable and well controlled hypertension (BP normally 160/95 for at least 3 months); b) asthma (no serious attacks in the past year); c) hypothyroidism (T4 within normal limits for at least 1 year); and d) Type II diabetes (subjects with a reported HgbA1c outside of normal limits within the last 6 months should be reviewed with the study site Investigator);
- Subject received ECT treatment within the last 6 months;
- Prior participation in a clinical trial of any other psychotropic medication within 2 months;
- Subjects with a history of treatment resistant schizophrenia;
- Subjects with a history of Tardive dyskinesia (TD) or Neuroleptic Malignant Syndrome (NMS) as determined clinically by the Investigator;
- Unwilling or unable to comply with the Lifestyle guidelines described in this Protocol;
- Subjects with implanted metal;
- Subjects with claustrophobia such that they are unable to tolerate MR scanning.
- Subjects taking medication that inhibit CYP3A4 or CYP2D6
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Pennsylvania
Philadelphia, Pennsylvania, 19104
About this study
Official title: A Phase1B Study: A Placebo Controlled Study of PF-03654746 Given as Add-On Treatment of Cognitive Deficits in Schizophrenia
This study will look at the impact of dosing as well as ongoing treatment with an investigation medication identified as PF-03654746, on cognitive and physiologic indicators of brain function. Data from this study will assist with the evaluation of the utility of functional magnetic resonance imaging, arterial spin labeling (ASL), and electrophysiologic measures in the detection of early signals of the effectiveness of medications developed to target cognitive impairment in schizophrenia. Safety and tolerability of PF-03654746 in this population will be also be evaluated.
- Conditions
- Schizophrenia
- Being tested
- PF 03654746, Placebo
- Keywords
- Schizophrenia, Cognitive Impairment, Electrophysiology, H3 receptor antagonist
- Medical subject headings
- Schizophrenia, Cognitive Dysfunction
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PF 03654746Drug
All participants will receive 3 weeks of PF-03654746 and 3 weeks of placebo. PF-03654746 and placebo will be administered in a flexible titration regimen, beginning with 0.5 mg/d. If 0.5 mg/d is well tolerated, the dose will be increased to 1.0 mg/d after 5 days. If 1.0 mg/d is not well tolerated, the dose will be decreased to 0.5 mg/d, with the goal of achieving a stable dose of PF-03654746 within the first two weeks of dosing and avoiding further dose changes during the final week of dosing.
PlaceboOther
Placebo will be used as a comparator to the active arm.
| Study group | Role | What they receive |
|---|---|---|
| PF-03654746 | Active comparator | H3 receptor antagonist currently being developed for the treatment of cognitive impairment associated with schizophrenia (CIAS) as well as with Alzheimer's disease. Receives: Drug: PF 03654746 |
| Placebo | Placebo comparator | Not described Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
MATRICS Consensus Cognitive Battery
Measured: 13 - 15 Weeks
Secondary outcomes (3)
ASL perfusion and performance on neurocognitive measures
Measured: 3 Weeks
fMRI activation parameters and performance on neurocognitive measures.
Measured: 3 weeks
ERP measures and performance on neurocognitive measures
Measured: 3 Weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 May 2011 (estimated)
- Study startApr 2009
- Primary completionNov 2010
- Study completionNov 2010
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for SchizophreniaStudies of the same condition, open and under way.
- More trials run by University of PennsylvaniaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 16 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Pennsylvania
- Sponsor type
- University, hospital or other
- Collaborators
- Pfizer
- Investigators
- Raquel P. Gur, M.D., Ph.D., Principal investigator, University of Pennsylvania
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01346163
- Sponsor's protocol ID
- 809087
- Status last verified
- Apr 2011
- First submitted
- 20 May 2009
- Last updated
- 2 May 2011
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 2 May 2011. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase1B Study: A Placebo Controlled Study of PF-03654746 Given as Add-On Treatment of Cognitive Deficits in Schizophrenia
- ClinicalTrials.gov ID
- NCT01346163
- Acronym / sponsor ID
- 809087
- Conditions
- Schizophrenia
- Keywords
- Schizophrenia, Cognitive Impairment, Electrophysiology, H3 receptor antagonist
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 16 participants (actual)
- Lead sponsor
- University of PennsylvaniaUniversity, hospital or other
- Collaborators
- Pfizer
- Study start
- Apr 2009
- Primary completion
- Nov 2010 (actual)
- Study completion
- Nov 2010 (actual)
- First posted
- 2 May 2011 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study will look at the impact of dosing as well as ongoing treatment with an investigation medication identified as PF-03654746, on cognitive and physiologic indicators of brain function. Data from this study will assist with the evaluation of the utility of functional magnetic resonance imaging, arterial spin labeling (ASL), and electrophysiologic measures in the detection of early signals of the effectiveness of medications developed to target cognitive impairment in schizophrenia. Safety and tolerability of PF-03654746 in this population will be also be evaluated.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| PF-03654746 | Active comparator | Drug: PF 03654746H3 receptor antagonist currently being developed for the treatment of cognitive impairment associated with schizophrenia (CIAS) as well as with Alzheimer's disease. |
| Placebo | Placebo comparator | Other: Placebo |
Who may qualify
- Ages
- 18 to 40 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (20 listed)
- Subjects must be competent to provide informed consent to participate in a clinical trial before any trial-related procedures can take place;
- Subjects must be willing and able to comply with scheduled visits, treatments, laboratory tests and other testing and study procedures;
- Subjects who participate must be willing to remain in-patient for at least one week at the beginning of each treatment period and remain in the hospital until judged by the Investigator to be clinically stable and able to be discharged to outpatient status;
- Subjects must be fluent in English and able to understand all study related materials;
- Subjects must be between the ages of 18-40 (inclusive) and if Female be of non-childbearing potential;
Key exclusion criteria (39 listed)
- Female subjects who still have child bearing potential and females who are breastfeeding;
- History of febrile illness within 5 days prior to the first dose;
- Any condition possibly affecting drug absorption (eg, gastrectomy);
- Subjects who have a positive urine drug screen which cannot be explained by prescribed medications;
- History of regular alcohol consumption exceeding 7 drinks/week for females or 14 drinks/week for men (1 drink = 5 ounces (150 mL) of wine or 12 ounces (360 mL) of beer or 1.5 ounces (45 mL) of hard liquor) within 6 months of screening;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PF 03654746All participants will receive 3 weeks of PF-03654746 and 3 weeks of placebo. PF-03654746 and placebo will be administered in a flexible titration regimen, beginning with 0.5 mg/d. If 0.5 mg/d is well tolerated, the dose will be increased to 1.0 mg/d after 5 days. If 1.0 mg/d is not well tolerated, the dose will be decreased to 0.5 mg/d, with the goal of achieving a stable dose of PF-03654746 within the first two weeks of dosing and avoiding further dose changes during the final week of dosing. | Drug | PF-03654746 |
| PlaceboPlacebo will be used as a comparator to the active arm. | Other | Placebo |
Primary outcome
MATRICS Consensus Cognitive Battery
Time frame: 13 - 15 Weeks
3 secondary outcomes
ASL perfusion and performance on neurocognitive measures
Time frame: 3 Weeks
fMRI activation parameters and performance on neurocognitive measures.
Time frame: 3 weeks
ERP measures and performance on neurocognitive measures
Time frame: 3 Weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 May 2011.
- University of Pennsylvania Department of Neuropsychiatry Home PageLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Raquel P. Gur, M.D., Ph.D. principal investigator
University of Pennsylvania
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing PF 03654746 in people with Schizophrenia, run by University of Pennsylvania at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 20 inclusion and 39 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 2 May 2011. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
MATRICS Consensus Cognitive Battery (time frame: 13 - 15 Weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 May 2011.