A Study to Evaluate the Pharmacokinetics Of Sativex® in Subjects With Severe Renal Impairment or End Stage Renal Disease, Compared to Matched Subjects With Normal Renal Function.

NCT02325024 | Withdrawn Phase 1

• 2 other identifiers: GWCP14262014-003104-67
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

The study aims to determine the pharmacokinetic (PK) profile of a single oromucosal dose of Sativex® (i.e. how the body absorbs, distributes, metabolises and excretes the drug) when subjects have severe renal impairment or end stage renal disease (ESRD), compared with subjects who have normal renal function. The primary clinical hypothesis is that there will be an effect from severe renal impairment on the PK of Sativex® when administered as a single oromucosal dose. The study additionally aims to evaluate the safety and tolerability of the same single oromucosal dose of Sativex® in subjects with severe renal impairment or ESRD.

Conditions

Renal Insufficiency; Kidney Disease

Keywords

Sativex; GW-1000-02; Nabiximols; Pharmacokinetics; Renal Insufficiency; Chronic Kidney Failure

Outcome Measures

Primary Outcomes (4)

• Pharmacokinetic parameters of THC: Cmax, AUC(0-t) and AUC(0-∞)

  The following are presented for THC: * Mean maximum (peak) plasma concentration of the drug (Cmax) * Mean area under the concentration-time curve calculated to the last observable concentration at time t (AUC(0-t)) * Mean area under the concentration-time curve from time zero to infinity (AUC(0-∞))

  Pre-dose (t=0) and up to 48 hours post-dose

• Pharmacokinetic parameters of 11-hydroxy-THC (11-OH-THC): Cmax, AUC(0-t) and AUC(0-∞)

  The following are presented for 11-OH-THC: * Mean Cmax * Mean AUC(0-t) * Mean AUC(0-∞)

  Pre-dose (t=0) and up to 48 hours post-dose

• Pharmacokinetic parameters of CBD: Cmax, AUC(0-t) and AUC(0-∞)

  The following are presented for CBD: * Mean Cmax * Mean AUC(0-t) * Mean AUC(0-∞)

  Pre-dose (t=0) and up to 48 hours post-dose

• Pharmacokinetic parameters of 7-hydroxy-CBD (7-OH-CBD): Cmax, AUC(0-t) and AUC(0-∞)

  The following are presented for 7-OH-CBD: * Mean Cmax * Mean AUC(0-t) * Mean AUC(0-∞)

  Pre-dose (t=0) and up to 48 hours post-dose

Secondary Outcomes (13)

• Pharmacokinetic parameters of THC: t(1/2), tmax, CL/F, CLr and F(e,u)

  Pre-dose (t=0) and up to 48 hours post-dose

• Pharmacokinetic parameters of 11-OH-THC: t(1/2), tmax, CLr and F(e,u)

  Pre-dose (t=0) and up to 48 hours post-dose

• Pharmacokinetic parameters of CBD: t(1/2), tmax, CL/F, CLr and F(e,u)

  Pre-dose (t=0) and up to 48 hours post-dose

• Pharmacokinetic parameters of 7-OH-CBD: t(1/2), tmax, CLr and F(e,u)

  Pre-dose (t=0) and up to 48 hours post-dose

• Pharmacokinetic parameters of THC: Cmax(u), AUC(0-t(u)), AUC(0-∞(u)) and CLu/F

  Pre-dose (t=0) and up to 48 hours post-dose

Study Arms (2)

Renally Impaired Subjects

EXPERIMENTAL

Treatment group consists of subjects with severe renal impairment or ESRD and in accordance with the following criteria; * Clinically significantly abnormal creatinine and creatinine clearance (CLcr \<30 mL/min) and not requiring dialysis. * Onset of renal impairment must have been documented at least 3 months prior to study start.

Drug: Sativex

Matched subjects with Normal Renal Function

EXPERIMENTAL

Group consists of healthy subjects (as determined by medical history, physical examination, biochemistry, hematology, urinalysis, hepatitis B and C, and HIV testing) who demonstrate normal renal function (CLcr \> 80 mL/min) and are individually matched to renally impaired subjects with respect to age (within the decile or five years, whichever is less), gender, and Body Mass Index (BMI) (+/- 10% BMI).

Drug: Sativex

Interventions

Sativex DRUG

Each 100 uL actuation (spray) of Sativex contains 27 mg/mL THC and 25 mg/mL CBD plus peppermint flavouring. The study dosage of 10.8 mg THC and 10 mg CBD is delivered as four sprays to the oral mucosa.

Also known as: GW-1000-02, Nabiximols, THC/CBD spray

Matched subjects with Normal Renal Function; Renally Impaired Subjects

Eligibility Criteria

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

You may qualify if:

• Willing and able to give written informed consent for participation in the study.
• Male or female aged 18 years or above.
• Able (in the investigator's opinion) and willing to comply with all study requirements.
• Willing and able to communicate with the investigator.
• Vital signs at screening (after five minutes resting measured in the supine position) within the following ranges:
• Body temperature between 35.0-37.5°C
• Systolic blood pressure, 90-150 mmHg\*
• Diastolic blood pressure, 60-90 mmHg\*
• Pulse rate, 40-99 beats per minute (bpm)\*. \*Blood pressure and pulse rate will be taken again in a standing position. After two minutes standing, there shall be no more than a 20 mmHg drop in systolic or 10 mmHg drop in diastolic blood pressure, associated with clinical manifestation of postural hypotension.
• Have a body weight of at least 50.0 kg and have a body mass index (BMI) between 19.0 and 35.0 kg/m2, inclusive.
• Willing for his or her name to be notified to the responsible authorities for participation in this study, as applicable in individual countries.
• Willing to allow his or her primary care practitioner and consultant to be notified of participation in the study.
• Severe renal impairment or ESRD \[clinically significantly abnormal creatinine and creatinine clearance (CLcr \<30 mL/min and not requiring dialysis\].
• Onset of renal impairment must be documented at least 3 months prior to study start.
• In good health as determined by medical history, physical examination, biochemistry, hematology, urinalysis, hepatitis B and C, and HIV testing.

You may not qualify if:

• Subjects meeting any of the following criteria will not be eligible for this trial:
• Donation or loss of 400 mL or more of blood within eight weeks prior to dosing and unwilling to abstain from donation of blood during the study.
• Significant concomitant illness within the two weeks prior to dosing.
• At high risk for requiring hospital admission or extended hospital stay during study period or any scheduled elective hospitalization during the planned study duration.
• Requiring dialysis or expected to require dialysis during study period.
• Has any surgical or medical condition, significant disease or disorder or any finding on physical examination and/or oral examination (other than their underlying condition) which might significantly alter the absorption, distribution, metabolism or excretion of drugs or that, in the opinion of the investigator, may put the subject at risk, influence the result of the study, or the subject's ability to participate in the study.
• History of renal transplant.
• Clinical evidence of acute or chronic liver disease or liver injury as indicated by clinically significant abnormal liver function tests such as Aspartate Aminotransferase, Alanine Aminotransferase, gamma glutamyl-transpeptidase, alkaline phosphatase (any ≥2.5 x Upper Limit of Normal \[ULN\] ) or serum bilirubin (≥1.5 x ULN) unless there is another likely explanation (e.g. Gilbert's syndrome).
• Any change in medication within 14 days prior to dosing or planned for anytime throughout the study which might significantly alter the absorption, distribution, metabolism or excretion of the Investigational Medicinal Product (IMP), in the opinion of the investigator.
• Any known or suspected hypersensitivity to cannabinoids or any of the excipients of the IMP(s).
• Positive result for the presence of HBsAg, HCAb, or HIV antibodies.
• Currently using or has used cannabis and/or cannabinoid-based medications (e.g. Marinol®, Nabilone®, Cannador®) within 30 days of study entry and unwilling to abstain for the duration of the study.
• Any known or suspected history of a substance abuse/dependence disorder within the 12 months prior to dosing or current use of an illicit drug or current non prescribed use of any prescription drug, or evidence of such abuse as indicated by the laboratory assays conducted during the screening or baseline evaluations.
• Current heavy alcohol consumption (more than 60 g of pure alcohol per day for men, and more than 40 g of pure alcohol per day for women).
• Unwilling to abstain from drinking alcohol for 24 hours prior to each visit and during the inpatient period of the study.

Sponsors & Collaborators

• GW Pharmaceuticals Ltd: lead

MeSH Terms

Conditions

Renal Insufficiency; Kidney Diseases; Marijuana Abuse; Kidney Failure, Chronic

Interventions

nabiximols

Condition Hierarchy (Ancestors)

Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders; Renal Insufficiency, Chronic; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 19, 2014
• First Posted: December 24, 2014
• Study Start: January 1, 2016
• Primary Completion: October 1, 2016
• Study Completion: October 1, 2016
• Last Updated: August 11, 2016

Record last verified: 2016-08