Study to Evaluate the Effect of AFQ056 in Obsessive Compu... | NCT01813019

NCT01813019

Status Module

Description Module

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
AFQ056	Experimental	Following baseline, approximately 60 patients who are considered eligible will be randomized to AFQ056 arm and will receive the dosing regimen of 4 weeks AFQ056 b.i.d up-titration period of 50 mg,100 mg, 150 mg and 200 mg , followed by 12 weeks AFQ056 200 mg fixed dose* and then a 3 week down-titration of 100 mg, 50 mg and 25 mg AFQ056 b.i.d) *patients that do not tolerate 200 mg b.i.d may be down-titrated to 150 mg b.i.d.	Drug: AFQ056
Placebo	Placebo Comparator	Following baseline, approximately 60 patients who are considered eligible will be randomized to Placebo arm and will receive the dosing regimen of 4 weeks Placebo b.i.d up-titration period of 50 mg,100 mg, 150 mg and 200 mg , followed by 12 weeks Placebo 200 mg fixed dose* and then a 3 week down-titration of 100 mg, 50 mg and 25 mg Placebo b.i.d) *patients that do not tolerate 200 matching placebo AFQ056 mg b.i.d may be down-titrated to 150 mg b.i.d.	Drug: Placebo

Name	Type	Description	Arm Group Labels	Other Names
AFQ056	Drug	mGluR5 antagonist	AFQ056	Mavoglurant

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
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.	baseline, week 17

Secondary Outcomes

Measure	Description	Time Frame
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.	16 weeks

Eligibility Module

Eligibility Criteria

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.

Name	Affiliation	Role
Novartis Pharmaceuticals	Novartis Pharmaceuticals	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Novartis Investigative Site		San Diego	California	92103	United States
Novartis Investigative Site

PubMed Identifier	Type	Citation	Retractions
28044255	Derived	Rutrick D, Stein DJ, Subramanian G, Smith B, Fava M, Hasler G, Cha JH, Gasparini F, Donchev T, Ocwieja M, Johns D, Gomez-Mancilla B. Mavoglurant Augmentation in OCD Patients Resistant to Selective Serotonin Reuptake Inhibitors: A Proof-of-Concept, Randomized, Placebo-Controlled, Phase 2 Study. Adv Ther. 2017 Feb;34(2):524-541. doi: 10.1007/s12325-016-0468-5. Epub 2017 Jan 2.

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Placebo	Matching Placebo b.i.d. dosing
FG001	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

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

ID	Title	Description
BG000	Placebo	Matching Placebo b.i.d. dosing
BG001	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
BG002	Total	Total of all reporting groups

Units	Counts
Participants	BG00024 BG00126 BG00250

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

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.

Pharmacodynamics (PD) analysis set only participants that were analyzed at baseline and Week 17. Positive change from baseline indicates a decrease in symptom severity

Posted

Least Squares Mean

Standard Error

Scores on a scale

baseline, week 17

ID	Title	Description
OG000	Placebo	Matching Placebo b.i.d. dosing
OG001	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

Units	Counts
Participants	OG00017 OG00121

Title

Denominators

Categories

Title	Measurements
	OG000-8.0± 1.78 OG001-6.9± 1.75

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001		Mixed Models Analysis		0.671													No	Superiority or Other

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.

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.

Posted

16 weeks

ID	Title	Description
OG000	Placebo	Matching Placebo b.i.d. dosing
OG001	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

Units	Counts
Participants	OG000

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Atrial fibrillation	Cardiac disorders	MedDRA	Systematic Assessment	EG0001 affected24 at risk EG0010 affected26 at risk
Otitis media	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected24 at risk EG0011 affected26 at risk
Face injury	Injury, poisoning and procedural complications	MedDRA	Systematic Assessment	EG0001 affected24 at risk EG0010 affected26 at risk
Head injury	Injury, poisoning and procedural complications	MedDRA	Systematic Assessment	EG0001 affected24 at risk EG0010 affected26 at risk
Limb injury	Injury, poisoning and procedural complications	MedDRA	Systematic Assessment	EG0001 affected24 at risk EG0010 affected26 at risk
VIIth nerve paralysis	Nervous system disorders	MedDRA	Systematic Assessment	EG0000 affected24 at risk EG0011 affected26 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Bradycardia	Cardiac disorders	MedDRA	Systematic Assessment	EG0002 affected24 at risk EG0010 affected26 at risk
Vertigo	Ear and labyrinth disorders	MedDRA	Systematic Assessment	EG0001 affected24 at risk EG0012 affected26 at risk
Abdominal pain upper	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0001 affected24 at risk EG0012 affected26 at risk
Dyspepsia	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0000 affected24 at risk EG0012 affected26 at risk
Fatigue	General disorders	MedDRA	Systematic Assessment	EG0001 affected24 at risk EG0012 affected26 at risk
Nasopharyngitis	Infections and infestations	MedDRA	Systematic Assessment	EG0004 affected24 at risk EG0012 affected26 at risk
Aspartate aminotransferase increased	Investigations	MedDRA	Systematic Assessment	EG0001 affected24 at risk EG0012 affected26 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA	Systematic Assessment	EG0000 affected24 at risk EG0012 affected26 at risk
Disturbance in attention	Nervous system disorders	MedDRA	Systematic Assessment	EG0000 affected24 at risk EG0012 affected26 at risk
Dizziness	Nervous system disorders	MedDRA	Systematic Assessment	EG0002 affected24 at risk EG0015 affected26 at risk
Headache	Nervous system disorders	MedDRA	Systematic Assessment	EG0008 affected24 at risk EG00110 affected26 at risk
Migraine	Nervous system disorders	MedDRA	Systematic Assessment	EG0000 affected24 at risk EG0012 affected26 at risk
Abnormal dreams	Psychiatric disorders	MedDRA	Systematic Assessment	EG0001 affected24 at risk EG0012 affected26 at risk
Agitation	Psychiatric disorders	MedDRA	Systematic Assessment	EG0000 affected24 at risk EG0012 affected26 at risk
Depression	Psychiatric disorders	MedDRA	Systematic Assessment	EG0002 affected24 at risk EG0011 affected26 at risk
Insomnia	Psychiatric disorders	MedDRA	Systematic Assessment	EG0002 affected24 at risk EG0016 affected26 at risk

ID	Term
D009771	Obsessive-Compulsive Disorder
D009770	Obsessive Behavior
D003192	Compulsive Behavior

ID	Term
D001008	Anxiety Disorders
D001523	Mental Disorders
D001526	Behavioral Symptoms
D001519	Behavior
D007175	Impulsive Behavior

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Placebo	Matching Placebo b.i.d. dosing			2	24	15	24
EG001	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			1	26	18	26