A Study of the Safety and Tolerability of GWP42006 in Healthy Subjects

NCT01918735 | Completed Phase 1 DMC

• 1 other identifier: GWEP1303
• Study Type: interventional
• Target: 66
• Locations: 1 country
• Sites: 1

Brief Summary

The primary objective of this study is to evaluate the safety and tolerability of single ascending (increasing) and multiple doses of GWP42006 compared with placebo.

Conditions

Epilepsy

Keywords

Safety; Tolerability; Assessment of potential adverse events; Assessment of potential laboratory abnormalities

Outcome Measures

Primary Outcomes (1)

• The incidence of adverse events as measure of subject safety

  The number of subjects who experienced an adverse event during each arm of the study is presented.

  Day 0 - Day 10

Secondary Outcomes (3)

• To determine the plasma concentration time curves for GWP42006, 7-hydroxy-GWP42006 and 6-hydroxy-GWP42006 compounds, following escalating single doses and multiple doses of pure GWP42006.

  Pre-dose then 0, 0.04, 0.08, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 24, 36, 48 h post-dose

• To investigate cognitive function following single ascending and multiples doses of GWP42006

  Admission (Day -1) and 2 h post-dose

• To investigate gene expression following multiple doses of GWP42006

  Pre-dose on multiple dose Days 1-4 then 2 h post-dose on multiple dose Day 5

Study Arms (10)

Group/dose level 1a

EXPERIMENTAL

25 mg GWP42006 oral solution. As a safety precaution, subjects will be split into two sub-groups for sentinel dosing. On the first day of dosing , only two subjects will be dosed (randomisation schedule designed so that one placebo one active will be dosed on first day). Following a review of the safety data for the first set of subjects, the remaining subjects will be dosed.

Drug: GWP42006

Group/dose level 1b

PLACEBO COMPARATOR

Matching placebo for Group/dose level 1a. As a safety precaution, subjects will be split into two sub-groups for sentinel dosing. On the first day of dosing , only two subjects will be dosed (randomisation schedule designed so that one placebo one active will be dosed on first day). Following a review of the safety data for the first set of subjects, the remaining subjects will be dosed.

Drug: Placebo

Group/dose level 2a

EXPERIMENTAL

75 mg GWP42006 oral solution. As a safety precaution, subjects will be split into two sub-groups for sentinel dosing. On the first day of dosing , only two subjects will be dosed (randomisation schedule designed so that one placebo one active will be dosed on first day). Following a review of the safety data for the first set of subjects, the remaining subjects will be dosed.

Drug: GWP42006

Group/dose level 2b

PLACEBO COMPARATOR

Matching placebo for Group/dose level 2a. As a safety precaution, subjects will be split into two sub-groups for sentinel dosing. On the first day of dosing , only two subjects will be dosed (randomisation schedule designed so that one placebo one active will be dosed on first day). Following a review of the safety data for the first set of subjects, the remaining subjects will be dosed.

Drug: Placebo

Group/dose level 3a

EXPERIMENTAL

200 mg GWP42006 oral solution (single dose) followed by an intravenous administration of 5 mg GWP42006 after the oral dose

Drug: GWP42006

Group/dose level 3b

PLACEBO COMPARATOR

Matching placebo for Group/dose level 3a

Drug: Placebo

Group/dose level 4a

EXPERIMENTAL

400 mg GWP42006 oral solution

Drug: GWP42006

Group/dose level 4b

PLACEBO COMPARATOR

Matching placebo for Group/dose level 4a

Drug: Placebo

GWP42006 1, 2, or 3 times daily

EXPERIMENTAL

Subjects will receive the selected dose of GWP42006 once, twice or three times daily (the number of daily doses and actual dose will be decided upon based on results from Part 1 of the study) for a total of 5 days, with the final dose given on the morning of Day 5.

Drug: GWP42006

Placebo 1, 2, or 3 times daily

PLACEBO COMPARATOR

Subjects will receive placebo once, twice or three times daily (the number of daily doses and actual dose will be decided upon based on results from Part 1 of the study) for a total of 5 days, with the final dose given on the morning of Day 5.

Drug: Placebo

Interventions

Placebo DRUG

Placebo control matched to the oral or intravenous experimental comparator drug

Also known as: Placebo control

Group/dose level 1b; Group/dose level 2b; Group/dose level 3b; Group/dose level 4b; Placebo 1, 2, or 3 times daily

GWP42006 DRUG

Oral administration of 25 (Group/dose level 1a and 1b), 75 (Group/dose level 2a and 2b), 200 (Group/dose level 3a and 3b) and 400 mg GWP42006 (Group/dose level 4a and 4b), provided as 50 mg/mL GWP42006 solution in sesame oil containing flavourings and sweetener, for dilution on the day of dosing, as required. Additional intravenous administration of 5 mg GWP42006 and 10 mL Solutol HS 15 solution to Group/dose level 3a and 3b subjects.

GWP42006 1, 2, or 3 times daily; Group/dose level 1a; Group/dose level 2a; Group/dose level 3a; Group/dose level 4a

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Healthy females of non-childbearing potential or healthy males
• Age 18 to 65 years, inclusive
• Body mass index of 18 to 30 kg/m2 inclusive or, if outside the range, considered not clinically significant by the investigator
• Must have no clinically significant abnormal findings on physical examination, vital signs, electrocardiogram, medical history, or clinical laboratory results during screening or Day -1 (admission)
• Must be willing and able to communicate and participate in the whole study
• Must provide written informed consent
• Must be willing to allow his or her primary care practitioner and consultant, if appropriate, to be notified of participation in the study
• Must agree to use an adequate method of contraception: Two or more of the following methods are acceptable and must include at least one barrier method:
• Surgical sterilisation (i.e. bilateral tubal ligation, hysterectomy for female partners; vasectomy for males)
• Placement of an intrauterine device or intrauterine system
• Hormonal contraception (implantable, patch, oral)
• Barrier methods (for male subjects, this must be a condom; for female subjects, either their partner's use of a condom or the subject's use of an occlusive cap \[diaphragm or cervical/vault caps\] with spermicidal foam/gel/film/cream/suppository).
• Alternatively, true abstinence is acceptable when it is in line with the subject's preferred and usual lifestyle.

You may not qualify if:

• Participation in a clinical research study/receiving an Investigational Medicinal Product within the 3 months prior to screening
• Subjects who are study site employees, or immediate family members of a study site or sponsor employee
• Subjects who have previously been randomised in this study
• History of any drug or alcohol abuse in the past 2 years, or current habituation to any medications or illegal drugs
• Regular alcohol consumption in males \>21 units per week and females \>14 units per week (1 unit = 0.5 pint beer, 25 mL of 40% spirit or a 125 mL glass of wine)
• Tobacco product use in the previous 6 months. A breath carbon monoxide reading of greater than 10 ppm at screening
• Subjects who do not have suitable veins for multiple venepunctures/cannulation as assessed by the investigator at screening
• Clinically significant abnormal clinical chemistry, haematology or urinalysis as judged by the investigator
• Positive drugs of abuse test result
• Positive hepatitis B surface antigen, hepatitis C virus antibody or human immunodeficiency virus-1 and -2 results
• History of clinically relevant physical abnormalities, medical conditions or clinical laboratory test results e.g. cardiovascular, renal, hepatic, pulmonary, haematological, endocrinological, neurological, psychiatric, chronic respiratory or gastrointestinal disease as judged by the investigator
• Clinically relevant symptoms or a clinically significant illness in the 4 weeks prior to screening
• Known cardiovascular condition or history of a cardiovascular condition or clinically relevant abnormalities in the 12-lead electrocardiogram measured at screening
• Subject has a postural drop of 20 mmHg or more in systolic blood pressure at screening, with features of postural hypotension, in the opinion of the investigator
• Concurrent cardiovascular conditions, which will, in the investigators opinion, interfere with the ability to read their electrocardiograms

Sponsors & Collaborators

• Jazz Pharmaceuticals: lead

Study Sites (1)

Quotient Clinical

Nottingham, NG11 6JS, United Kingdom

Location

MeSH Terms

Conditions

Epilepsy

Condition Hierarchy (Ancestors)

Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 1, 2013
• First Posted: August 8, 2013
• Study Start: August 1, 2013
• Primary Completion: December 1, 2013
• Study Completion: December 1, 2013
• Last Updated: December 20, 2022

Record last verified: 2022-12

Locations

GB (1)