GWMD09126 - GWP42003:GWP42004 antipsychotic(s) weight gain treatment

• Register: EUCTR
• Last refreshed on: 22 October 2012
• Main ID: EUCTR2011-000180-28-GB
• Date of registration: 11/04/2011
• Prospective Registration: Yes
• Primary sponsor: GW Pharma Ltd
• Public title: GWMD09126 - GWP42003:GWP42004 antipsychotic(s) weight gain treatment
• Scientific title: A randomised, double-blind, placebo-controlled parallel group, pilot study of 40:1 ratio of formulated GWP42003 : GWP42004 in the treatment of iatrogenic weight gain and dyslipidaemia associated with olanzapine or other antipsychotic(s) treatment in subjects with schizophrenia or other non-affective psychosis.
• Date of first enrolment: 12/07/2011
• Target sample size: 60
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2011-000180-28
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: yes Other trial design description: Pilot Study If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 2

Countries of recruitment

United Kingdom

Contacts

• Name: GW Pharma Ltd. Switchboard
• Affiliation: GW Pharma Ltd.

• Name: GW Pharma Ltd. Switchboard
• Affiliation: GW Pharma Ltd.

Key inclusion & exclusion criteria

Inclusion criteria:
For inclusion in the study subjects must fulfil ALL of the following criteria:
- Willing and able to give informed consent for participation in the study.
- Subject is aged 18 years or above.
- Diagnosis (DSM-IV-TR) of schizophrenia, or other non-affective psychosis.
- Receiving at least one antipsychotic.
- The dose of antipsychotic(s) is stable for at least 2 weeks prior to randomisation (Visit 2).
- Subject is willing to maintain a stable dose of antipsychotic(s) for the duration of the study.
- Evidence of recent weight gain attributable to antipsychotic treatment (in the opinion of the Investigator), prior to screening (Visit 1). Wherever possible, investigator must exclude other possible causes of weight gain, such as change in exercise, diet , concomitant medications or other illnesses.
- Each subject must have a further documented 2% weight gain attributable to antipsychotic treatment in the baseline period (between Visits 1 and 2).
- Willing to maintain a stable dose of any concomitant medications (excluding PRN medicines at the Investigator’s discretion), and have been on a stable dose for a minimum of 6 weeks prior to screening (Visit 1) (with the exception of antipsychotic(s)).
- No changes in diet or exercise for 6 weeks prior to screening (Visit 1) and subject agrees to maintain stability, for the duration of the study (in the opinion of the investigator).
- Capable of complying with the study requirements and completing the study (in the opinion of the investigator).
-Willing to allow his or her primary care practitioner and consultant, if appropriate, to be notified of participation in the study.

Are the trial subjects under 18? no
Number of subjects for this age range: 0
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 57
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 3

Exclusion criteria:
The subject may not enter the study if ANY of the following apply:
- Subject has Axis I (DSM-IV-TR) diagnosis of schizoaffective disorder.
- Subject has drug induced or toxic psychosis (in the opinion of the investigator).
- Subject presents with a clinical picture and/or history that is consistent with:
- Delirium, dementia, amnesia or other cognitive disorder.
- Bipolar disorder or major depression.
- Subject has a significant history of anxiety, suicidal ideation or self-harm based on history or routine psychiatric status examination (in the opinion of the investigator).
- Subject has an unstable thyroid pathology (including hypo or hyperthyroidism), within the past six months (in the opinion of the investigator).
- Subject has a history of neuroleptic malignant syndrome.
- Subject requires or has had electroconvulsive therapy (ECT) treatment in the 2 month period prior to randomisation (Visit 2).
- Subject has a clinical diagnosis of diabetes.
- Any known or suspected history of (in the opinion of the investigator):
- Alcohol or substance abuse;
- Epilepsy or recurrent seizures.
- Any known or suspected history of depression sufficient to require treatment or disrupt ordinary life (excluding episodes of reactive depression - in the opinion of the investigator).
- BDI Score = 19 (at Visit 1 or 2).
- Clinically significant cardiac, renal or hepatic impairment in the opinion of the investigator.
- Genetic dyslipidaemic condition in the opinion of the investigator.
- Female subject who is pregnant, lactating or planning pregnancy during the course of the study and for 3 months from the date of last dose.
- Female subjects of child bearing potential, unless willing to use two forms of contraception, one of which must be a barrier contraception (e.g. Female condom of occlusive cap (diaphragm or cervical vault/caps) with spermicide) during the study and for 3 months from the date of last dose (however a male condom should not be used in conjunction with the female condom).
- Male subjects whose partner is of child bearing potential, unless willing to use an appropriate barrier method of contraception (condom and spermicide) in addition to having their female partner use another form of barrier contraception (e.g. occlusive cap (diaphragm or cervical vault/caps) with spermicide) during the study and for 3 months from date of last dose (however a male condom should not be used in conjunction with a female condom).
- Received an Investigational Medicinal Product within the 90 days before the screening visit (Visit 1).
- In the opinion of the investigator, is not considered to be suitable for the study.
- Poor compliance as observed during screening period.
- Any other significant disease or disorder which, in the opinion of the investigator, may either put the subject at risk because of participation in the study, influence the result of the study, or the subject's ability to participate in the study.
- Any abnormalities identified during the physical examination at Visit 1 that in the opinion of the investigator would prevent the subject from safe participation in the study.
- Unwilling to abstain from donation of blood during the study.
- Previously randomised into this study.



Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Iatrogenic weight gain and dyslipidaemia associated with treatment using antipsychotic medication
MedDRA version: 14.1 Level: LLT Classification code 10058110 Term: Dyslipidemia System Organ Class: 10027433 - Metabolism and nutrition disorders
MedDRA version: 14.1 Level: LLT Classification code 10047896 Term: Weight gain System Organ Class: 10022891 - Investigations

Therapeutic area: Diseases [C] - Nutritional and Metabolic Diseases [C18]

Intervention(s)

Product Name: GWP42003 Capsule
Product Code: EN0012
Pharmaceutical Form: Capsule, hard
Current Sponsor code: GWP42003
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 100-
Pharmaceutical form of the placebo: Capsule, hard
Route of administration of the placebo: Oral use

Product Name: GWP42004 Capsule
Product Code: EN0011
Pharmaceutical Form: Capsule, hard
Current Sponsor code: GWP42004
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 5-
Pharmaceutical form of the placebo: Capsule, hard
Route of administration of the placebo: Oral use

Primary Outcome(s)

Primary end point(s): To evaluate the efficacy of a 40:1 ratio of GWP42003 : GWP42004 compared with placebo in the change in body weight from baseline in subjects treated with antipsychotic(s) for schizophrenia or other non-affective psychosis

Main Objective: To evaluate the efficacy of a 40:1 ratio of GWP42003 : GWP42004 compared with placebo in the change in body weight from baseline in subjects treated with olanzapine or other antipsychotic(s) in subjects with schizophrenia or other non-affective psychosis.

Secondary Objective: To evaluate the efficacy of a 40:1 ratio of GWP42003 : GWP42004 compared with placebo on:
Lipid parameters; Glucose Control (fasted); Insulin Control (fasted); Glycosylated haemoglobin A1c (HbA1c); Adipose tissue distribution; Markers of adipocyte function including leptin and adiponectin; Markers of inflammation including cytokines and C-Reactive Protein (CRP); Hormonal markers including prolactin; Endocannabinoid plasma levels; Positive symptoms of schizophrenia; Negative symptoms of schizophrenia; General symptoms of schizophrenia; Physician’s global impression of illness severity; Subject’s quality of life; Assessment of symptoms of depression; Assessment of extrapyramidal symptoms; Assessment of mood; Assessment of appetite.
To assess the safety and tolerability of a 40:1 ratio of GWP42003 : GWP42004 compared with placebo on:
Adverse events (AE); Vital Signs; Electrocardiogram (ECG); Laboratory findings; Physical examination.

Timepoint(s) of evaluation of this end point: 6 weeks post treatment

Secondary Outcome(s)

Secondary end point(s): To evaluate the effect of a 40:1 ratio of GWP42003 : GWP42004 compared with placebo on:

Body Fat Parameters:
- Change from baseline to end of treatment in skin fold thickness measurements;
- Change from baseline to end of treatment in waist to hip ratio;

Lipid Parameters:
- Change from baseline to end of treatment in serum Total Cholesterol;
- Change from baseline to end of treatment in serum LDL Cholesterol;
- Change from baseline to end of treatment in serum HDL Cholesterol;
- Change from baseline to end of treatment in serum HDL / LDL Cholesterol ratio;
- Change from baseline to end of treatment in serum HDL / Total Cholesterol ratio;
- Change from baseline to end of treatment in serum Triglycerides;
- Change from baseline to end of treatment in serum apolipoprotein markers (ApoA & ApoB);
- Change from baseline to end of treatment in serum Apo A/Apo B ratio;
- Change from baseline to end of treatment in serum non-esterified (“free”) fatty acids to the end of treatment;

Glucose Control:
- Change from baseline to end of treatment in glucose control parameters (fasting plasma glucose);
- Change from baseline to end of treatment in HbA1c (whole blood);

Insulin Control:
- Change from baseline to end of treatment in insulin control parameters (fasting serum insulin);

Psychiatric/Clinical Assessments:
Change from baseline to end of treatment in the following assessments:
- Positive and Negative Syndrome Scale (PANSS) ‘P’; ‘N’; ‘G’;
- Global Assessment of Functioning (GAF);
- Beck Depression Inventory (BDI);
- UWIST Mood Adjective Checklist (UMACL);
- Simpson-Angus Scale (SAS);
- End of treatment assessment of Clinician’s Global Impression of Change (CGIC);

Hormonal Marker:
- Change from baseline to end of treatment in serum prolactin concentration;

Markers of Inflammation:
- Change from baseline to end of treatment in serum CRP and serum cytokines (including TNF-a, IL-6 and IL-2);

Markers of adipocyte function:
- Change from baseline to end of treatment in serum leptin and adiponectin concentrations;

Endocannabinoid Levels- where facilities allow:
- Change from baseline in endocannabinoid plasma levels to the end of treatment;

Appetite Assessments:
- Change from baseline in mean appetite NRS score (taken from the last 7 days of baseline period (days -7 to 0) to the end of treatment (taken from last 7 days of treatment period);

Safety Endpoints:
To assess the safety and tolerability of a 40:1 ratio of CBD : THCV compared with placebo on:
- AEs;
- Vital signs;
- ECG;
- Laboratory findings;
- Physical examination.

Timepoint(s) of evaluation of this end point: 6 weeks post treatment

Secondary ID(s)

GWMD09126

Source(s) of Monetary Support

GW Pharma Ltd.