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A Long-term Safety Study of Cannabidiol Oral Solution (GWP42003-P, CBD-OS) in Patients With Rett Syndrome

Primary Purpose

Rett Syndrome, RTT

Status

Terminated

Phase

Phase 3

Locations

International

Study Type

Interventional

Intervention

GWP42003-P

About this trial

This is an interventional treatment trial for Rett Syndrome focused on measuring Cannabidiol, CBD, Epidiolex, GWP42003-P

Eligibility Criteria

2 Years - 18 Years (Child, Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Participant has completed all scheduled visits of the treatment phase of the randomized controlled trial (RCT), GWND18064 (NCT03848832), and has transitioned to open-label extension (OLE) by the point of RCT follow-up
Participant (if possessing adequate understanding, in the investigator's opinion) and/or the participant(s)/legal representative is willing and able to give informed consent/assent for participation in the trial.
Participant and the participant's caregiver are willing and able (in the investigator's opinion) to comply with all trial requirements (including the completion of all caregiver assessments by the same caregiver throughout the trial).
Ability to swallow the investigational medicinal product (IMP) provided as a liquid solution, or the ability for the IMP to be delivered via gastrostomy (G) or nasogastric (NG) feeding tube (only G- or NG-tubes made from polyurethane or silicon are allowed).
Participant and/or parent(s)/legal representative is willing to allow the responsible authorities to be notified of participation in the trial, if mandated by local law.
Participant and/or parent(s)/legal representative is willing to allow the participant's primary care practitioner (if the participant has one) and consultant (if the participant has one) to be notified of participation in the trial, if the primary care practitioner/consultant is different from the investigator.

Exclusion Criteria:

Participant meets the withdrawal criteria (including clinically significant abnormal laboratory values), in the investigator's opinion.
Participant met during the RCT the criteria for permanent IMP discontinuation (unless in the case of an adverse event [AE], if the AE was not considered related with the IMP; participants that met alanine aminotransferase (ALT)/aspartate aminotransferase (AST) elevations discontinuation criteria must be excluded).
Females of childbearing potential, unless willing to ensure that they or their partner use a highly effective method of birth control (e.g., combined [estrogen and progestogen containing] hormonal contraception associated with inhibition of ovulation [oral, intravaginal, or transdermal], progestogen-only hormonal contraception associated with inhibition of ovulation [oral, injectable, or implantable], intrauterine devices/hormone-releasing systems, bilateral tubal occlusion, vasectomized partner, sexual abstinence during the trial and for 3 months after the last dose
Participant has been previously enrolled and dosed in this trial.
Participant is unwilling to abstain from donation of blood during the trial.
Male participants who are fertile (i.e., after puberty unless permanently sterile by bilateral orchidectomy) and with a partner of childbearing potential unless agree to ensure that they use male contraception (e.g., condom) or remain sexually abstinent during the trial and for 3 months after the last dose

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

GWP42003-P

Arm Description

100 milligrams per milliliter (mg/mL) GWP42003-P oral solution, taken twice daily (morning and evening).

Outcomes

Primary Outcome Measures

Number of Participants With Any Treatment-emergent Adverse Events (TEAEs), Discontinuations Due to AEs, Serious AEs, and Treatment-related AEs

Adverse events (AEs) were defined as any new unfavorable/unintended signs/symptoms (including abnormal laboratory findings when relevant) or diagnosis or worsening of a pre-existing condition that occurs during the study. TEAEs were defined as the AEs that started or worsened in severity or seriousness following the first dose of GWP42003-P. A serious AE was defined as any AE that results in any of the following outcomes: death, life-threatening adverse experience, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability/incapacity, congenital anomaly/birth defect, or cancer, any other experience that suggests a significant hazard, contraindication, side effect or precaution that may require medical or surgical intervention to prevent one of the outcomes listed above, or an event that changes the risk/benefit ratio of the study.

Number of Participants With Treatment-emergent Clinical Laboratory Parameters From the Baseline at Any Time Post-dose

Treatment-emergent clinical parameters were defined as the following: Treatment-emergent alanine transferase (ALT) > 3×upper limit of normal (ULN), > 5×ULN and > 8×ULN; Treatment-emergent aspartate aminotransferase (AST) > 3×ULN, > 5×ULN and > 8×ULN; Treatment-emergent ALT or AST > 3×ULN, > 5×ULN and > 8×ULN; Treatment-emergent ALT or AST > 3×ULN and either bilirubin > 2×ULN or international normalized ratio (INR) > 1.5.

Number of Participants With Potentially Clinically Significant Changes in Vital Sign Values of Blood Pressure From the Baseline at Any Time Post-dose

Potentially clinically significant vital sign values of blood pressure (BP) were defined as sitting systolic BP (mmHg) change: < -20 or > 20 mmHg and sitting diastolic BP change: < -10 or > 10 mmHg. Vital sign measurements were taken in a sitting position at rest for 5 minutes. Blood pressure readings were recorded using the same arm throughout the trial, when possible.

Number of Participants With Clinically Significant Changes in the Vital Sign Values of Pulse Rate From the Baseline at Any Time Post-dose

Potentially clinically significant vital sign values of pulse rate were defined as pulse rate change: < -10 or > 10 beats per minute. Vital sign measurements were taken in a sitting position at rest for 5 minutes.

Number of Participants With Clinically Significant Percent Change in Body Weight From the Baseline at Any Time Post-dose

Clinically significant body weight changes were defined as the percent change in body weight (≤7% change or ≥7% change).

Number of Participants With At Least One Post Open Label Extension Baseline Flagged ECG Result

Electrocardiogram assessments were performed for QTcB and QTcF >450 msec, >480 msec, and >500 msec. QTcB = corrected QT interval with Bazette correction. QTcF = QTc corrected by Fridericia.

Number of Participants With Any Changes In Menstruation Cycle at Any Time Post-dose

Participants were evaluated for any changes to typical menstrual cycles, duration of menstrual cycles, and typical strength of the menstrual cycles during the study.

Number of Participants With Suicidal Ideation or Behavior at the Baseline and at Any Time Post-dose

Suicidal ideation and behavior was assessed by the investigator via a clinical interview with the caregiver. The questionnaire included following questions: Has the child expressed any wish to be dead?, Has the child made any suicide attempts?, Has the child shown any non-suicidal self-injurious behavior? The responses were recorded as Yes/No.

Mean Change From Baseline in Insulin-like Growth Factor-1 (IGF-1) Levels at End of Treatment

Blood samples were collected to assess changes in serum IGF-1 levels. A negative mean change from baseline indicates a reduction in IGF-1 levels.

Number of Participants With Changes in Tanner Staging at the Baseline and at End of Treatment

Pubic hair growth and breast development of all adolescents were assessed by the investigator or caregiver using Tanner Staging categorization from 1 to 5. Stage 1- No glandular tissue; areola follows skin contours of chest; No pubic hair Stage 2- Breast bud forms; areola begins to widen; a small amount of long, downy hair with slight pigmentation on labia majora Stage 3- Breast begins to become more elevated and extends beyond borders of the areola, which continues to widen but remains in contour with surrounding breast; Hair becomes more coarse and curly and begins to extend laterally Stage 4- Increased breast size and elevation; areola and papilla form a secondary mound projecting from the contour of the surrounding breast; Adult-like hair quality, extending across pubis but sparing medial thighs Stage 5- Breast reaches final adult size; areola returns to the contour of the surrounding breast, with a projecting central papilla; Hair extends to medial surface of the thigh.

Secondary Outcome Measures

Mean Change From Baseline in Rett Syndrome Behaviour Questionnaire (RSBQ) Overall Score at End of Treatment

RSBQ is a caregiver-completed questionnaire that assesses the overall condition (45 items) in individuals with Rett Syndrome. Each item is rated on a 3-point scale (0-2); 0 indicating an item that is "not true as far as you know," 1 indicating an item is "somewhat or sometimes true," and 2 indicating an item that is "very true or often true". " Item 31 ("Uses eye gaze to convey feelings, needs and wishes") is reverse-scored (0 indicating "very true or often true", 1 indicating "somewhat or sometimes true," and 2 indicating "not true as far as you know"). The total summed score ranges from 0 to 90, with higher scores representing greater severity. A negative mean change from baseline indicates an improvement in overall condition.

Mean Clinical Global Impressions-Improvement (CGI-I) Continuous Score at End of Treatment

CGI-I is a 7-point scale that requires the clinician to assess whether a patient's condition has improved or worsened relative to a baseline state at the beginning of the intervention. This was rated as: 1 = very much improved; 2 = much improved; 3 = minimally improved; 4 = no change; 5 = minimally worse; 6 = much worse; or 7 = very much worse. The mean continuous CGI-I score (averaged from each treatment enrolled under protocol and under annex) at Visit 14 (Day 729) is being reported. Higher mean scores indicate worse condition.

Mean Clinician Global Impressions - Severity Scale (CGI-S) Continuous Score at End of Treatment

CGI-S is a 7-point scale that requires the clinician to rate the severity of the participant's illness at the time of assessment relative to the clinician's experience with participants who had the same diagnosis. This was rated as: 1 = normal, not at all ill; 2 = borderline ill; 3 = mildly ill; 4 = moderately ill; 5 = markedly ill; 6 =severely ill; or 7 = extremely ill. The mean continuous CGI-S score (averaged from each treatment enrolled under protocol and under annex) at Visit 14 (Day 729) is being reported. Higher scores indicate more severe disease.

Mean Change From Baseline in Children's Sleep Habits Questionnaire (CSHQ) Total Score at End of Treatment

CSHQ is a caregiver-completed sleep screening instrument designed for school-aged children; which includes 33 items within 8 subscales:bedtime resistance (score range 6-18), sleep onset delay (range 1-3), sleep duration (range 3-9), sleep anxiety (range 4-12), night wakings (range 3-9), parasomnias (range 7-21), sleep-disordered breathing (range 3-9), daytime sleepiness (range 8-24). The 33 items range from 1 to 3, where 3="usually" (≥5 times/week), 2="sometimes" (2-4 times/week), and 1="rarely" (≤1 time/week); for items 31 and 32, 3=fall asleep, 2=very sleepy, 1=not sleepy. A score of 3 indicates greater severity; however, 6 items (1-Goes to bed at same time; 3-Falls asleep in own bed; 26-Wakes by himself; 2-Falls asleep in 20 minutes; 10-Sleeps the right amount; 11-Sleeps same amount each day) are reverse scored. The total summed score ranges from 33 to 99, with higher scores indicating disturbed sleep behavior. A negative mean change from baseline indicates improvement in sleep.

Mean Change From Baseline in 9-item Motor Behavioral Assessment (MBA-9) Total Score at End of Treatment

MBA-9 is derived from the full MBA scale (37 Rett syndrome symptoms) by selecting the items deemed amenable to change and which reflected areas of meaningful clinical change. The MBA-9 includes 9 items (Regression of motor skills; Poor eye/social contact; Lack of sustained interest; Does not reach for objects or people; Chewing difficulties; Speech disturbance; Hand clumsiness; Dystonia; and Hypertonia/rigidity). For each item, the severity of current symptoms is rated by the investigator on a 5-point numerical scale ranging from 0 to 4 with higher scores representing greater severity (0 = normal or never; 1 = mild or rare; 2 = moderate or occasional; 3 = marked or frequent; 4 = very severe or constant). Total MBA-9 score was calculated by summing the scores of 9 different subscale items. The total summed score ranges from 0 to 36, with higher scores representing greater severity. A negative mean change from baseline indicates improvement in behavior.

Full Information

NCT ID

NCT04252586

First Posted

January 30, 2020

Last Updated

July 12, 2022

Sponsor

Jazz Pharmaceuticals

Collaborators

GW Pharmaceuticals

1. Study Identification

Unique Protocol Identification Number

NCT04252586

Brief Title

A Long-term Safety Study of Cannabidiol Oral Solution (GWP42003-P, CBD-OS) in Patients With Rett Syndrome

Official Title

An Open-label Extension Trial to Investigate the Long-term Safety of Cannabidiol Oral Solution (GWP42003-P, CBD-OS) in Patients With Rett Syndrome

Study Type

Interventional

2. Study Status

Record Verification Date

July 2022

Overall Recruitment Status

Terminated

Why Stopped

Study was terminated due to COVID-19 pandemic and recruitment challenges in the parent study (GWND18064 - NCT03848832).

Study Start Date

February 28, 2020 (Actual)

Primary Completion Date

June 9, 2021 (Actual)

Study Completion Date

June 9, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Jazz Pharmaceuticals

Collaborators

GW Pharmaceuticals

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

Brief Summary

This study will be conducted to evaluate the long-term safety of cannabidiol oral solution (GWP42003-P, CBD-OS) in participants with Rett syndrome.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Rett Syndrome, RTT

Keywords

Cannabidiol, CBD, Epidiolex, GWP42003-P

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 3

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

21 (Actual)

8. Arms, Groups, and Interventions

Arm Title

GWP42003-P

Arm Type

Experimental

Arm Description

100 milligrams per milliliter (mg/mL) GWP42003-P oral solution, taken twice daily (morning and evening).

Intervention Type

Drug

Intervention Name(s)

GWP42003-P

Other Intervention Name(s)

Cannabidiol, CBD, Epidiolex, CBD-OS

Intervention Description

GWP42003-P presented as an oral solution containing cannabidiol in the excipients sesame oil with anhydrous ethanol, sweetener (sucralose), and strawberry flavoring

Primary Outcome Measure Information:

Title

Number of Participants With Any Treatment-emergent Adverse Events (TEAEs), Discontinuations Due to AEs, Serious AEs, and Treatment-related AEs

Description

Time Frame

Baseline of randomized controlled trial (RCT) Visit 1 (Day 1) up to Visit 16 (Day 767) in the OLE

Title

Number of Participants With Treatment-emergent Clinical Laboratory Parameters From the Baseline at Any Time Post-dose

Description

Time Frame

Baseline of randomized controlled trial (RCT) Visit 1 (Day 1) up to Visit 14 (Day 729) in the OLE

Title

Number of Participants With Potentially Clinically Significant Changes in Vital Sign Values of Blood Pressure From the Baseline at Any Time Post-dose

Description

Time Frame

Baseline of randomized controlled trial (RCT) Visit 1 (Day 1) up to Visit 15 (Day 739) in the OLE

Title

Number of Participants With Clinically Significant Changes in the Vital Sign Values of Pulse Rate From the Baseline at Any Time Post-dose

Description

Time Frame

Baseline of randomized controlled trial (RCT) Visit 1 (Day 1) up to Visit 15 (Day 739) in the OLE

Title

Number of Participants With Clinically Significant Percent Change in Body Weight From the Baseline at Any Time Post-dose

Description

Clinically significant body weight changes were defined as the percent change in body weight (≤7% change or ≥7% change).

Time Frame

Baseline of randomized controlled trial (RCT) Visit 1 (Day 1) up to Visit 14 (Day 729) in the OLE

Title

Number of Participants With At Least One Post Open Label Extension Baseline Flagged ECG Result

Description

Electrocardiogram assessments were performed for QTcB and QTcF >450 msec, >480 msec, and >500 msec. QTcB = corrected QT interval with Bazette correction. QTcF = QTc corrected by Fridericia.

Time Frame

Visit 4 (Day 29) up to Visit 15 (Day 739) in the OLE

Title

Number of Participants With Any Changes In Menstruation Cycle at Any Time Post-dose

Description

Participants were evaluated for any changes to typical menstrual cycles, duration of menstrual cycles, and typical strength of the menstrual cycles during the study.

Time Frame

Baseline of randomized controlled trial (RCT) Visit 1 (Day 1) up to Visit 14 (Day 729) in the OLE

Title

Number of Participants With Suicidal Ideation or Behavior at the Baseline and at Any Time Post-dose

Description

Time Frame

Baseline of randomized controlled trial (RCT) Visit 1 (Day 1) up to Visit 14 (Day 729) in the OLE

Title

Mean Change From Baseline in Insulin-like Growth Factor-1 (IGF-1) Levels at End of Treatment

Description

Blood samples were collected to assess changes in serum IGF-1 levels. A negative mean change from baseline indicates a reduction in IGF-1 levels.

Time Frame

Baseline of randomized controlled trial (RCT) Visit 1 (Day 1) up to Visit 14 (Day 729) in the OLE

Title

Number of Participants With Changes in Tanner Staging at the Baseline and at End of Treatment

Description

Time Frame

Baseline of randomized controlled trial (RCT) Visit 1 (Day 1) up to Visit 14 (Day 729) in the OLE

Secondary Outcome Measure Information:

Title

Mean Change From Baseline in Rett Syndrome Behaviour Questionnaire (RSBQ) Overall Score at End of Treatment

Description

Time Frame

Baseline of randomized controlled trial (RCT) Visit 1 (Day 1) up to Visit 14 (Day 729) in the OLE

Title

Mean Clinical Global Impressions-Improvement (CGI-I) Continuous Score at End of Treatment

Description

Time Frame

Visit 14 (Day 729) in the OLE

Title

Mean Clinician Global Impressions - Severity Scale (CGI-S) Continuous Score at End of Treatment

Description

Time Frame

Visit 14 (Day 729) in the OLE

Title

Mean Change From Baseline in Children's Sleep Habits Questionnaire (CSHQ) Total Score at End of Treatment

Description

Time Frame

Baseline of randomized controlled trial (RCT) Visit 1 (Day 1) up to Visit 14 (Day 729) in the OLE

Title

Mean Change From Baseline in 9-item Motor Behavioral Assessment (MBA-9) Total Score at End of Treatment

Description

Time Frame

Baseline of randomized controlled trial (RCT) Visit 1 (Day 1) up to Visit 14 (Day 729) in the OLE

10. Eligibility

Sex

All

Minimum Age & Unit of Time

2 Years

Maximum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Participant has completed all scheduled visits of the treatment phase of the randomized controlled trial (RCT), GWND18064 (NCT03848832), and has transitioned to open-label extension (OLE) by the point of RCT follow-up Participant (if possessing adequate understanding, in the investigator's opinion) and/or the participant(s)/legal representative is willing and able to give informed consent/assent for participation in the trial. Participant and the participant's caregiver are willing and able (in the investigator's opinion) to comply with all trial requirements (including the completion of all caregiver assessments by the same caregiver throughout the trial). Ability to swallow the investigational medicinal product (IMP) provided as a liquid solution, or the ability for the IMP to be delivered via gastrostomy (G) or nasogastric (NG) feeding tube (only G- or NG-tubes made from polyurethane or silicon are allowed). Participant and/or parent(s)/legal representative is willing to allow the responsible authorities to be notified of participation in the trial, if mandated by local law. Participant and/or parent(s)/legal representative is willing to allow the participant's primary care practitioner (if the participant has one) and consultant (if the participant has one) to be notified of participation in the trial, if the primary care practitioner/consultant is different from the investigator. Exclusion Criteria: Participant meets the withdrawal criteria (including clinically significant abnormal laboratory values), in the investigator's opinion. Participant met during the RCT the criteria for permanent IMP discontinuation (unless in the case of an adverse event [AE], if the AE was not considered related with the IMP; participants that met alanine aminotransferase (ALT)/aspartate aminotransferase (AST) elevations discontinuation criteria must be excluded). Females of childbearing potential, unless willing to ensure that they or their partner use a highly effective method of birth control (e.g., combined [estrogen and progestogen containing] hormonal contraception associated with inhibition of ovulation [oral, intravaginal, or transdermal], progestogen-only hormonal contraception associated with inhibition of ovulation [oral, injectable, or implantable], intrauterine devices/hormone-releasing systems, bilateral tubal occlusion, vasectomized partner, sexual abstinence during the trial and for 3 months after the last dose Participant has been previously enrolled and dosed in this trial. Participant is unwilling to abstain from donation of blood during the trial. Male participants who are fertile (i.e., after puberty unless permanently sterile by bilateral orchidectomy) and with a partner of childbearing potential unless agree to ensure that they use male contraception (e.g., condom) or remain sexually abstinent during the trial and for 3 months after the last dose

Facility Information:

Facility Name

Clinical Trial Site

City

Birmingham

State/Province

Alabama

ZIP/Postal Code

35294-0021

Country

United States

Facility Name

Clinical Trial Site

City

La Jolla

State/Province

California

ZIP/Postal Code

92093

Country

United States

Facility Name

Clinical Trial Site

City

Aurora

State/Province

Colorado

ZIP/Postal Code

80045

Country

United States

Facility Name

Clinical Trial Site

City

Chicago

State/Province

Illinois

ZIP/Postal Code

60612

Country

United States

Facility Name

Clinical Trial Site

City

Baltimore

State/Province

Maryland

ZIP/Postal Code

21205

Country

United States

Facility Name

Clinical Trial Site

City

Boston

State/Province

Massachusetts

ZIP/Postal Code

02115

Country

United States

Facility Name

Clinical Trial Site

City

Saint Paul

State/Province

Minnesota

ZIP/Postal Code

55101

Country

United States

Facility Name

Clinical Trial Site

City

Saint Louis

State/Province

Missouri

ZIP/Postal Code

63110-1093

Country

United States

Facility Name

Clinical Trial Site

City

Bronx

State/Province

New York

ZIP/Postal Code

10467

Country

United States

Facility Name

Clinical Trial Site

City

Cincinnati

State/Province

Ohio

ZIP/Postal Code

45229

Country

United States

Facility Name

Clinical Trial Site

City

Philadelphia

State/Province

Pennsylvania

ZIP/Postal Code

19104

Country

United States

Facility Name

Clinical Trial Site

City

Greenwood

State/Province

South Carolina

ZIP/Postal Code

29646

Country

United States

Facility Name

Clinical Trial Site

City

Nashville

State/Province

Tennessee

ZIP/Postal Code

37232

Country

United States

Facility Name

Clinical Trial Site

City

Houston

State/Province

Texas

ZIP/Postal Code

77030

Country

United States

Facility Name

Clinical Trial Site

City

Perth

Country

Australia

Facility Name

Clinical Trial Site

City

South Brisbane

Country

Australia

Facility Name

Clinical Trial Site

City

Toronto

Country

Canada

Facility Name

Clinical Trial Site

City

Vancouver

Country

Canada

Facility Name

Clinical Trial Site

City

Genova

Country

Italy

Facility Name

Clinical Trial Site

City

Messina

Country

Italy

Facility Name

Clinical Trial Site

City

Milano

Country

Italy

Facility Name

Clinical Trial Site

City

Rome

Country

Italy

Facility Name

Clinical Trial Site

City

Siena

Country

Italy

Facility Name

Clinical Trial Site #1

City

Barcelona

Country

Spain

Facility Name

Clinical Trial Site #2

City

Barcelona

Country

Spain

Facility Name

Clinical Trial Site #1

City

Madrid

Country

Spain

Facility Name

Clinical Trial Site #2

City

Madrid

Country

Spain

Facility Name

Clinical Trial Site

City

Valencia

Country

Spain

Facility Name

Clinical Trial Site

City

Edinburgh

Country

United Kingdom

Facility Name

Clinical Trial Site

City

Liverpool

Country

United Kingdom

Facility Name

Clinical Trial Site

City

London

Country

United Kingdom

12. IPD Sharing Statement

Plan to Share IPD

Learn more about this trial

A Long-term Safety Study of Cannabidiol Oral Solution (GWP42003-P, CBD-OS) in Patients With Rett Syndrome

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A Long-term Safety Study of Cannabidiol Oral Solution (GWP42003-P, CBD-OS) in Patients With Rett Syndrome

Rett Syndrome, RTT

About this trial

Eligibility Criteria

Sites / Locations

Arms of the Study

Arm 1

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

1. Study Identification

2. Study Status

3. Sponsor/Collaborators

4. Oversight

5. Study Description

6. Conditions and Keywords

7. Study Design

8. Arms, Groups, and Interventions

10. Eligibility

12. IPD Sharing Statement

Learn more about this trial