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A Study of GWP42003 as Adjunctive Therapy in the First Line Treatment of Schizophrenia or Related Psychotic Disorder

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ClinicalTrials.gov Identifier: NCT02006628
Recruitment Status : Completed
First Posted : December 10, 2013
Last Update Posted : February 23, 2017
Sponsor:
Information provided by (Responsible Party):
GW Research Ltd

Brief Summary:
A study to compare the change in symptom severity in patients with schizophrenia or related psychotic disorder when treated with GWP42003 or placebo, added to existing anti-psychotic therapy over a period of six weeks. Secondary objectives are to evaluate the effect of GWP42003 on quality of life and cognition and to assess the safety and tolerability of GWP42003.

Condition or disease Intervention/treatment Phase
Schizophrenia Schizophrenia-related Psychotic Disorder Drug: Placebo Drug: GWP42003 Phase 2

  Show Detailed Description

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 88 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Double-blind, Randomised, Placebo-controlled, Parallel Group Study of GWP42003 as Adjunctive Therapy in First Line Treatment of Schizophrenia or Related Psychotic Disorder
Study Start Date : February 2014
Actual Primary Completion Date : January 2015
Actual Study Completion Date : January 2015

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Placebo Comparator: Placebo

Placebo oral solution is presented as an oily solution containing excipients, sesame oil, ethanol, sucralose and strawberry flavouring.

Dose: 5 mL Placebo oral solution to be taken twice daily for 6 weeks.

The total dose administered within any 24-hour interval will be 10 mL of oral solution.

Drug: Placebo
Patients will self-administer their allocated randomised treatment twice daily (in the morning and in the evening) for six weeks using the dosing spoons provided with each bottle. Study medication will be swallowed and may be taken with other concomitant medications, as directed by the investigator.
Other Name: Placebo control

Active Comparator: GWP42003

GWP42003 oral solution is presented as an oily solution containing 100 mg/mL of cannabidiol (CBD) dissolved in excipients, sesame oil, ethanol, sucralose and strawberry flavouring.

Dose: 5 mL GWP42003 (500 mg CBD) oral solution to be taken twice daily for 6 weeks.

The total dose administered within any 24-hour interval will be 10 mL of oral solution (1 g CBD).

Drug: GWP42003
Patients will self-administer their allocated randomised treatment twice daily (in the morning and in the evening) for six weeks using the dosing spoons provided with each bottle. Study medication will be swallowed and may be taken with other concomitant medications, as directed by the investigator.
Other Names:
  • Cannabidiol
  • Epidiolex




Primary Outcome Measures :
  1. Change from baseline to the end of treatment in Positive and Negative Syndrome Scale (PANSS) total score. [ Time Frame: 0-43 days ]
    The PANSS is a medical scale completed by a trained rater at site and is used for measuring symptom severity of patients with schizophrenia or related psychotic disorder. It is a 30 item rating instrument that assesses the positive and negative symptoms of schizophrenia as well as symptoms of general psychopathology. A PANSS total score is derived from the sum of the 30 items and the PANSS items are also grouped into three subscales: Positive ('P'), Negative ('N'), and General ('G'). Individual items are rated on a seven point scale, where 1 = absent and 7 = extreme. A decrease in total score indicates an improvement in condition.

  2. Change from baseline to the end of treatment in Positive and Negative Syndrome Scale (PANSS) 'P' score. [ Time Frame: 0-43 days ]
    The PANSS is a medical scale completed by a trained rater at site and is used for measuring symptom severity of patients with schizophrenia or related psychotic disorder. It is a 30 item rating instrument that assesses the positive and negative symptoms of schizophrenia as well as symptoms of general psychopathology. A PANSS total score is derived from the sum of the 30 items and the PANSS items are also grouped into three subscales: Positive ('P'), Negative ('N'), and General ('G'). Individual items are rated on a seven point scale, where 1 = absent and 7 = extreme. Changes in the Positive subscale of the PANSS are presented. A decrease in score indicates an improvement in condition.

  3. Change from baseline to the end of treatment in Positive and Negative Syndrome Scale (PANSS) 'N' score. [ Time Frame: 0-43 days ]
    The PANSS is a medical scale completed by a trained rater at site and is used for measuring symptom severity of patients with schizophrenia or related psychotic disorder. It is a 30 item rating instrument that assesses the positive and negative symptoms of schizophrenia as well as symptoms of general psychopathology. A PANSS total score is derived from the sum of the 30 items and the PANSS items are also grouped into three subscales: Positive ('P'), Negative ('N'), and General ('G'). Individual items are rated on a seven point scale, where 1 = absent and 7 = extreme. Changes in the Negative subscale of the PANSS are presented. A decrease in score indicates an improvement in condition.

  4. Change from baseline to the end of treatment in Positive and Negative Syndrome Scale (PANSS) 'G' score. [ Time Frame: 0-43 days ]
    The PANSS is a medical scale completed by a trained rater at site and is used for measuring symptom severity of patients with schizophrenia or related psychotic disorder. It is a 30 item rating instrument that assesses the positive and negative symptoms of schizophrenia as well as symptoms of general psychopathology. A PANSS total score is derived from the sum of the 30 items and the PANSS items are also grouped into three subscales: Positive ('P'), Negative ('N'), and General ('G'). Individual items are rated on a seven point scale, where 1 = absent and 7 = extreme. Changes in the General subscale of the PANSS are presented. A decrease in score indicates an improvement in condition.

  5. Change from baseline to the end of treatment in Scale for the Assessment of Negative Symptoms (SANS) total score. [ Time Frame: 0-43 days ]
    SANS assesses five symptom complexes to obtain clinical ratings of negative symptoms in patients with schizophrenia or related psychotic disorder. They are: affective blunting; alogia (impoverished thinking); avolition/apathy; anhedonia/asociality; and disturbance of attention. Assessments are conducted on a six-point scale (0 = not at all to 5 = severe). A decrease in score indicates an improvement in condition.

  6. Change in the severity of mental illness at the end of treatment relative to baseline using the Clinical Global Impressions - Severity Scale (CGI-S). [ Time Frame: 0-43 days ]

    The CGI-S is a seven point scale that requires the clinician to rate the severity of the patient's illness at the time of assessment, relative to the clinician's past experience with patients who have the same diagnosis. Considering total clinical experience, a patient will be assessed on severity of mental illness at the time of rating. The markers are:

    Not at all ill, Borderline mentally ill, Mildly ill, Moderately ill, Markedly ill, Severely ill, Extremely ill.

    The number of patients for each of the markers at the final study visit is presented.


  7. Improvement in mental illness at the end of treatment relative to baseline using the Clinical Global Impressions - Improvement Scale (CGI-I). [ Time Frame: 0-43 days ]

    The CGI-I is a seven point scale that requires the clinician to assess how much the patient's illness has improved or worsened relative to a baseline state at the beginning of the intervention. The markers are:

    Very much improved, Much improved, Minimally improved, No change, Minimally worse, Much worse, Very much worse.

    The number of patients for each of the markers at the final study visit is presented.


  8. Change from baseline to the end of treatment in Global Assessment of Functioning (GAF) score. [ Time Frame: 0-43 days ]

    The GAF is a numeric scale (0 through 100) used by mental health clinicians and physicians alike to subjectively rate the social, occupational, and psychological functioning of adults. The patient will be assigned a code related to the group that best describes the patient's functioning. Patients assigned the code 91-100 are deemed to have:

    "Superior functioning in a wide range of activities, life's problems never seem to get out of hand, is sought out by others because of his or her many positive qualities. No symptoms."

    Patients assigned the code 1-10 are deemed in:

    "Persistent danger of severely hurting self or others (e.g., recurrent violence) OR persistent inability to maintain minimal personal hygiene OR serious suicidal act with clear expectation of death."

    A decrease in score indicates an improvement in condition.


  9. Change from baseline to the end of treatment in Simpson-Angus Scale (SAS) total score. [ Time Frame: 0-43 days ]
    The SAS is a 10-item instrument used to evaluate the presence and severity of Parkinsonian symptomatology. The ten items focus on rigidity rather than bradykinesia, and do not assess subjective rigidity or slowness. Items are rated for severity on a 0-4 scale, where 0 is indicative of 'normal' and 4 being the most severe. Definitions are given for each anchor point within each item and a total score is obtained by summing over the 10 items. The 10 items that are scored are: Gait; Arm Dropping; Shoulder Shaking; Elbow Rigidity; Wrist Rigidity or Fixation of Position; Leg Pendulousness; Head Dropping; Glabella Tap; Tremor and Salivation. A decrease in score indicates an improvement in condition.

  10. Change from baseline to the end of treatment in Brief Assessment of Cognition in Schizophrenia (BACS) average score. [ Time Frame: 0-43 days ]
    The BACS is an instrument used to assess the aspects of cognition found to be most impaired and most strongly correlated with outcome in patients with schizophrenia or related psychotic disorder. The BACS consists of six domains: verbal memory; working memory; motor speed; verbal fluency; attention and speed information processing and executive functions. A score is obtained for each domain and a composite summary score is also calculated as the average of the scores from the six domains. An increase in score indicates an improvement in cognition.

  11. Carer Global Impression of Change (CGIC) in the patient's general functional ability and sleep at the end of treatment relative to baseline. [ Time Frame: 0-43 days ]

    If applicable, carers will be asked the following three questions to be rated on a seven-point scale:

    1. "How has the participant's general functional ability changed since Visit 1?"
    2. "How has the participant's quantity of sleep changed since Visit 1?"
    3. "How has the participant's quality of sleep changed since Visit 1?"

    The markers are: Very much worse, Much worse, Slightly worse, No change, Slightly improved, Much improved, Very much improved.

    The number of patients for each of the markers at the final study visit is presented.


  12. Participant Global Impression of Change (PGIC) in the patient's general functional ability and sleep at the end of treatment relative to baseline. [ Time Frame: 0-43 days ]

    Patients will be asked the following three questions to be rated on a seven-point scale:

    1. "How has your general functional ability changed since Visit 1?"
    2. "How has your quantity of sleep changed since Visit 1?"
    3. "How has your quality of sleep changed since Visit 1?"

    The markers are: Very much worse, Much worse, Slightly worse, No change, Slightly improved, Much improved, Very much improved.

    The number of patients for each of the markers at the final study visit is presented.


  13. Change in dependence disorder at the end of treatment relative to baseline. [ Time Frame: 0-43 days ]

    If applicable, patients will be asked if their dependence disorder has changed since baseline.

    The markers are: Remained the same, Increased, Decreased, Both (if the participant is using more than one substance, there may be both an increase and a decrease), Don't know.

    The number of patients for each of the markers at the final study visit is presented.



Secondary Outcome Measures :
  1. Change from baseline to the end of treatment in mean body weight. [ Time Frame: 0-43 days ]
    Body weight (kg) will be measured at baseline and at the end of treatment.

  2. Change from baseline to the end of treatment in mean waist circumference. [ Time Frame: 0-43 days ]
    Waist circumference will be measured at baseline and at the end of treatment.

  3. Change from baseline to the end of treatment in mean Body Mass Index (BMI). [ Time Frame: 0-43 days ]
    Individual subject's BMIs will be calculated at baseline and at the end of treatment by dividing mass (kg) by height (m2).

  4. Change from baseline to the end of treatment in mean serum High Density Lipoprotein (HDL)-Cholesterol (C) levels. [ Time Frame: 0-43 days ]
    Serum HDL-C levels will be measured in blood samples taken at baseline and at the end of treatment.

  5. Change from baseline to the end of treatment in mean serum bilirubin. [ Time Frame: 0-43 days ]
    Serum total bilirubin will be measured in blood samples taken at baseline and at the end of treatment as a measure of liver function.

  6. Change from baseline to the end of treatment in mean serum alkaline phosphatase levels. [ Time Frame: 0-43 days ]
    Serum alkaline phosphatase levels will be measured in blood samples taken at baseline and at the end of treatment as a measure of liver function.

  7. Change from baseline to the end of treatment in mean serum Aspartate Aminotransferase (AST) levels. [ Time Frame: 0-43 days ]
    Serum AST levels will be measured in blood samples taken at baseline and at the end of treatment as a measure of liver function.

  8. Change from baseline to the end of treatment in mean serum Alanine Aminotransferase (ALT) levels. [ Time Frame: 0-43 days ]
    Serum ALT levels will be measured in blood samples taken at baseline and at the end of treatment as a measure of liver function.

  9. Change from baseline to the end of treatment in mean serum Gamma-Glutamyl Transferase levels. [ Time Frame: 0-43 days ]
    Serum Gamma-Glutamyl Transferase levels will be measured in blood samples taken at baseline and at the end of treatment as a measure of liver function.

  10. Change from baseline to the end of treatment in mean serum Prolactin levels. [ Time Frame: 0-43 days ]
    Serum Prolactin levels will be measured in blood samples taken at baseline and at the end of treatment.

  11. Change from baseline to the end of treatment in mean serum C-Reactive Protein (CRP) levels. [ Time Frame: 0-43 days ]
    Serum CRP levels will be measured in blood samples taken at baseline and at the end of treatment as a measure of inflammation.

  12. Change from baseline to the end of treatment in mean serum Interleukin-2 (IL-2) levels. [ Time Frame: 0-43 days ]
    Serum IL-2 levels will be measured in blood samples taken at baseline and at the end of treatment as a measure of inflammation.

  13. Change from baseline to the end of treatment in mean serum Interleukin-6 (IL-6) levels. [ Time Frame: 0-43 days ]
    Serum IL-6 levels will be measured in blood samples taken at baseline and at the end of treatment as a measure of inflammation.

  14. Change from baseline to the end of treatment in mean serum Interferon gamma levels. [ Time Frame: 0-43 days ]
    Serum Interferon gamma levels will be measured in blood samples taken at baseline and at the end of treatment as a measure of inflammation.

  15. Change from baseline to the end of treatment in mean plasma cannabinoid levels. [ Time Frame: 0-43 days ]
    Plasma cannabinoid levels will be measured in blood samples taken at baseline and at the end of treatment as a measure of treatment compliance and dosage.

  16. Incidence of Adverse Events (AEs) as a measure of patient safety. [ Time Frame: 0-57 days ]
    The number of subjects who experience an AE during the course of the study will be presented. All reported AEs will be classified by system organ class and preferred term using the current Medical Dictionary for Regulatory Activities dictionary.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria (all must be fulfilled):

  • Patient is willing and able to give written informed consent for participation in the study and does not require involuntary treatment.
  • Patient is male or female aged 18 to 65 years.
  • Patient is able (in the investigator's opinion) and willing to comply with all study requirements.
  • Patient is diagnosed with schizophrenia or a related psychotic disorder (such as schizoaffective or schizophreniform disorder) as defined by the Diagnostic and Statistical Manual of Mental Disorders Version 4.
  • Patient must have been treated for a minimum of four-weeks and be on a stable dose of their current anti-psychotic (AP) medication.
  • Patient must have shown the capacity to respond at least partially to first line AP medication in the opinion of the investigator.
  • Patient must be able to remain stable on their dose of AP and concomitant medications for the duration of the study, in the opinion of the investigator.
  • Patient is willing for his or her name to be notified to the responsible authorities for participation in this study, as applicable in individual countries.
  • Patient is willing to allow his or her primary care practitioner and consultant, if appropriate, to be notified of participation in the study.

Exclusion Criteria (any of the following):

  • Any known or suspected hypersensitivity to cannabinoids or any of the excipients of the Investigational Medicinal Product.
  • Patient has a Positive and Negative Symptom Scale total score of < 60 at Visit 1.
  • Patient presents with a current clinical picture and/or history that is consistent with:

    i. delirium or dementia ii. acute drug induced psychosis iii. bipolar disorder

  • Patient is taking more the one AP medication during the study.
  • Female patients of child bearing potential and male patients whose partner is of child bearing potential, unless willing to ensure that they or their partner use effective contraception, for example, oral contraception, double barrier, intra-uterine device, during the study and for three months thereafter (however a male condom should not be used in conjunction with a female condom).
  • Female patient who is pregnant, lactating or planning pregnancy during the course of the study and for three months thereafter.
  • Patients who have received an Investigational Medicinal Product within 30 days prior to the screening visit.
  • Any other significant disease or disorder which, in the opinion of the investigator, may either put the patient at risk because of participation in the study, may influence the result of the study, or the patient's ability to participate in the study.
  • Following a physical examination, the patient has any abnormalities that, in the opinion of the investigator would prevent the patient from safe participation in the study.
  • Unwilling to abstain from donation of blood during the study.
  • Travel outside the country of residence planned during the study.
  • Patient previously randomised into this study.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02006628


Locations
Poland
Investigator 7
Bytomska, Poland
Investigator 4
Gdansk, Poland
Investigator 9
Katowice, Poland
Investigator 5
Kielce, Poland
Investigator 10
Lublin, Poland
Investigator 8
Wrocław, Poland
Romania
Investigator 11
Bucharest, Romania
Investigator 12
Bucharest, Romania
Investigator 15
Bucharest, Romania
Investigator 14
Sibiu, Romania
Investigator 16
Targoviste, Romania
Investigator 13
Targu Mures, Romania
United Kingdom
Investigator 2
Chertsey, United Kingdom
Investigator 1
Coventry, United Kingdom
Investigator 3
London, United Kingdom
Sponsors and Collaborators
GW Research Ltd
Investigators
Principal Investigator: Philip McGuire, MD PhD FRCPsych FMedSci Institute of Psychiatry, King's College London, De Crespigny Park, London, SE5 8AF, UK

Responsible Party: GW Research Ltd
ClinicalTrials.gov Identifier: NCT02006628     History of Changes
Other Study ID Numbers: GWAP1241
2013-000212-22 ( EudraCT Number )
First Posted: December 10, 2013    Key Record Dates
Last Update Posted: February 23, 2017
Last Verified: February 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Keywords provided by GW Research Ltd:
GWP42003
Cannabinoids
Schizophrenia

Additional relevant MeSH terms:
Disease
Schizophrenia
Mental Disorders
Psychotic Disorders
Pathologic Processes
Schizophrenia Spectrum and Other Psychotic Disorders