Failed SSRI Over 12 Weeks at Appropriate Doses, Patient Diagnosed With OCD and Resistant to SSRI Treatment
Conditions
Keywords
Obsessive compulsive disorder (OCD), obsessive fears, obsessions,, compulsions, OCD SSRI resistant
Brief summary
The purpose of this study is to determine whether AFQ056 as an add on therapy to SSRIs can have beneficial effects by reducing the total score of Y-BOCS (Yale and Brown Obsessive Compulsive Scale) in OCD patients resistant to SSRI treatment (failed SSRI over 12 weeks at appropriate doses).
Detailed description
This was a randomized, double-blind, parallel group, placebo-controlled, 12-weeks 200 mg b.i.d oral dose treatment of AFQ056 (following a 4 week up-titration period and followed by a 3 week down-titration period) or matched placebo in patients diagnosed with OCD and on background SSRI treatment for at least 12 weeks. Study was prematurely terminated at the time of the first Interim Analysis (IA) as the study did not meet its primary efficacy objective.
Interventions
DRUGAFQ056
mGluR5 antagonist
DRUGPlacebo
Matched placebo
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Male and female , non-smokers patients aged between 18 to 65 years (inclusive), * A primary diagnosis of obsessive-compulsive disorder (OCD) as per Diagnostic and Statistical Manual of Mental Disorders (DSM-IV-TR 4th ed, year 2000), as confirmed by an Independent Rater. * Be on a stable appropriate dose of selective serotonin reuptake inhibitor (SSRI) treatment for at least 12 weeks prior to Baseline. * Have an insufficient response to current SSRI treatment (as per Inclusion Criterion 4) and confirmed by an Independent Rater. * Have a Yale-Brown Obsessive Compulsive Scale (Y-BOCS) of score ≥ 16 at Screening (and confirmed by an Independent Rater). * Patient must have their eligibility confirmed following the remote interview conducted by the Independent Rater. * Able to communicate well with the investigator, to understand and comply with the requirements of the study.
Exclusion criteria
* Diagnosis of primary OCD symptom of hoarding. * Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using effective methods of contraception (not including oral contraceptives) during dosing and for 30 days after last dosing of study medication. * History of more than two unsatisfactory trials with different SSRI within a period of 2 years prior to screening (not including the current treatment with SSRI's given in an adequate dose for at least 12 weeks). * Diagnosed with any primary DSM-IV-TR Axis I disorder other than OCD (as confirmed by an Independent Rater); with the exception of depression. * History of eating disorder (e.g. anorexia, bulimia) according to DSMIV within the last 6 months prior to Screening, (as confirmed by an Independent Rater). * Diagnosed with antisocial personality disorder (DSM-IV-TR Axis II), as confirmed by an Independent Rater. * Has current or past medical history of bipolar disorder, schizophrenia or other psychotic disorders, schizoaffective disorder, autism or autistic spectrum disorders, borderline personality disorder, within the last 6 months prior to Screening. * Smokers (use of tobacco products in the previous 3 months). * History of hallucinations/psychosis that would require antipsychotic treatment or DSM-IV criteria being met * Score yes on item 4 or item 5 of the Suicidal Ideation section of the C-SSRS, if this ideation occurred in the past 6 months, or yes on any item of the Suicidal Behavior section, except for the Non- Suicidal Self-Injurious Behavior (item also included in the Suicidal Behavior section), if this behavior occurred in the past 2 years.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Yale - Brown Obsessive Compulsive Scale (Y-BOCS) Absolute Change From Baseline at Week 17 (End of 16-week Dosing). | baseline, week 17 | The Y-BOCS is a 10 item clinician-rated scale used to both determine the severity of OCD and to monitor symptom improvement throughout the course of the study. The Y-BOCS, specifically measures the severity of symptoms of OCD without being biased towards the type of obsessions or compulsions present. The scale includes questions about the amount of time spent on, how much impairment or distress experienced from, and how much resistance and control over these obsessive thoughts and compulsions. Each item is rated from 0 (no symptoms) to 4 (extreme symptoms) and yields a total possible score range from 0 to 40, with the following ranges indicating degree of severity: 0-7 = sub-clinical 8-15 = mild 16-23 = moderate 24-31 = severe 32-40 = extreme Baseline was compared to week 17 (end of week 16 dosing) to produce an absolute change. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Y-BOCS Reduction in Total Score From Baseline | 16 weeks | If a subject demonstrates at least 25% reduction in total Y-BOCS from Baseline then they will be classed as a responder whereas if a subject has a reduction in Y-BOCS of less than 25% then they will be categorized as a nonresponder. |
Countries
Bulgaria, Czechia, Germany, Switzerland, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo Matching Placebo b.i.d. dosing | 24 |
| AFQ056 AFQ056 b.i.d up-titration of 50mg,100mg, 150mg and 200 mg for 4 weeks then AFQ056 200mg b.i.d for 12 weeks and then a down-titration of AFQ056 100mg, 50mg and 25mg b.i.d for 3 weeks | 26 |
| Total | 50 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | administrative problems | 2 | 0 |
| Overall Study | Adverse Event | 0 | 3 |
| Overall Study | Protocol Deviation | 2 | 1 |
| Overall Study | Withdrawal by Subject | 3 | 2 |
Baseline characteristics
| Characteristic | Placebo | AFQ056 | Total |
|---|---|---|---|
| Age, Continuous | 39.9 years STANDARD_DEVIATION 10.06 | 41.3 years STANDARD_DEVIATION 13.27 | 40.6 years STANDARD_DEVIATION 11.74 |
| Gender Female | 13 Participants | 13 Participants | 26 Participants |
| Gender Male | 11 Participants | 13 Participants | 24 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 15 / 24 | 18 / 26 |
| serious Total, serious adverse events | 2 / 24 | 1 / 26 |
Outcome results
Primary
Yale - Brown Obsessive Compulsive Scale (Y-BOCS) Absolute Change From Baseline at Week 17 (End of 16-week Dosing).
The Y-BOCS is a 10 item clinician-rated scale used to both determine the severity of OCD and to monitor symptom improvement throughout the course of the study. The Y-BOCS, specifically measures the severity of symptoms of OCD without being biased towards the type of obsessions or compulsions present. The scale includes questions about the amount of time spent on, how much impairment or distress experienced from, and how much resistance and control over these obsessive thoughts and compulsions. Each item is rated from 0 (no symptoms) to 4 (extreme symptoms) and yields a total possible score range from 0 to 40, with the following ranges indicating degree of severity: 0-7 = sub-clinical 8-15 = mild 16-23 = moderate 24-31 = severe 32-40 = extreme Baseline was compared to week 17 (end of week 16 dosing) to produce an absolute change.
Time frame: baseline, week 17
Population: Pharmacodynamics (PD) analysis set only participants that were analyzed at baseline and Week 17. Positive change from baseline indicates a decrease in symptom severity
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Yale - Brown Obsessive Compulsive Scale (Y-BOCS) Absolute Change From Baseline at Week 17 (End of 16-week Dosing). | -8.0 Scores on a scale | Standard Error 1.78 |
| AFQ056 | Yale - Brown Obsessive Compulsive Scale (Y-BOCS) Absolute Change From Baseline at Week 17 (End of 16-week Dosing). | -6.9 Scores on a scale | Standard Error 1.75 |
p-value: 0.671Mixed Models Analysis
Secondary
Y-BOCS Reduction in Total Score From Baseline
If a subject demonstrates at least 25% reduction in total Y-BOCS from Baseline then they will be classed as a responder whereas if a subject has a reduction in Y-BOCS of less than 25% then they will be categorized as a nonresponder.
Time frame: 16 weeks
Population: The study was terminated due to an interim analysis of the primary efficacy outcome. Study was prematurely terminated at the time of the first Interim Analysis (IA) as the study did not meet its primary efficacy objective therefore secondary objective was not measured.