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Renal InsufficiencyPhase 1NCT02325024

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.

A Phase 1 study testing Sativex in people with Renal Insufficiency and Kidney Disease, run by GW Pharmaceuticals Ltd.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and olderHealthy volunteers can take part
Conditions the study is for
Renal Insufficiency, Kidney Disease
What is being tested?
Sativex
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
0 participants
Where
No sites listed yet
Study dates
Jan 2016to Oct 2016
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • Healthy volunteers accepted
  • Adult, Older adult

Who may be able to join

  • 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.
  • Creatinine clearance (CLcr) > 80 mL/min indicating normal renal function.
  • Individually matched to a renally impaired subject with respect to age (within the decile or 5 years, whichever is less), gender, and BMI (+/- 10% BMI).

Who cannot join

  • 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.
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  • 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.
  • Unwilling to abstain from nicotine products from midnight Day -2 to 48 hours post dose.
  • Unwilling to abstain from grapefruit products for one week prior to and throughout the inpatient period.
  • Consume more than five caffeinated beverages per day (e.g. five cups of tea or coffee or cans of cola) or who are unwilling to abstain from consumption of caffeine-containing food and beverages throughout the inpatient period.
  • Any known or suspected history or immediate family history of schizophrenia, or other psychotic illness, history of severe personality disorder or other severe significant psychiatric disorder other than depression associated with underlying condition.
  • Any history of epilepsy as evidenced by one or more seizures in the last 12 months.
  • Significant cardiac disease, or has a cardiac disorder that in the opinion of the investigator would put the subject at risk of a clinically relevant arrhythmia or myocardial infarction, or has a secondary or tertiary atrioventricular block, or evidence of clinically significant cardiac disease on ECG at screening.
  • Sexually active males whose partner is of childbearing potential who do not agree to practice two different methods of birth control or remain truly abstinent during the study and for three months after the last dose of study medication. Sexually active females of childbearing potential who do not agree to practice two different methods of birth control or remain truly abstinent during the study and for three months after the last dose of study medication. If employing birth control, two of the following precautions must be used: vasectomy, tubal ligation, vaginal diaphragm, intrauterine device, birth control pill, birth control implant, birth control depot injection, condom, or sponge with spermicide. However, a male condom must not be used in conjunction with a female condom as this may not prove effective.
  • Note: Non-childbearing potential is defined as female subjects who are surgically sterile (i.e., have undergone bilateral salpingo-oophorectomy, hysterectomy) and female subjects who have been postmenopausal for at least 12 consecutive months.
  • Pregnant, lactating or planning pregnancy during the course of the study and for three months thereafter.
  • Received an IMP within 30 days or five times the half-life of the IMP (whichever is greater) prior to the screening visit.
  • Travel outside the country of residence planned during the study.
  • Previously enrolled into this study or any other Sativex® study.

About this study

Official title: An Open-Label, Single-Dose Study to Compare the Pharmacokinetics (PK) of an Oromucosal Dose of Four Sprays of Sativex® in Subjects With Severe Renal Impairment or End Stage Renal Disease (ESRD), Not Requiring Dialysis, Compared to Matched Subjects With Normal Renal Function.

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.

Read the detailed description

This is a Phase I, open label, single-dose study to evaluate the effect of renal impairment on the PK of an oromucosal dose (four sprays) of Sativex® (containing 10.8 mg Δ9 tetrahydrocannabinol [THC] and 10 mg cannabidiol [CBD]) in subjects with severe renal impairment or ESRD (with a creatinine clearance < 30 mL/min and not requiring dialysis) compared to matched subjects with normal renal function (with a creatinine clearance > 80 mL/min).

Eligible subjects will be given a single oromucosal dose (four sprays) of Sativex® on Dosing Day 1. Serial blood and urine samples for determination of concentrations of THC, 11-hydroxy- Δ9 - tetrahydrocannabinol (11-OH-THC), CBD, and 7-hydroxy-cannabidiol (7- OH-CBD) will be collected from subjects with severe renal impairment or ESRD, not requiring dialysis, and matched subjects with normal renal function before and up to 48 hours after dosing at selected time points. Pre-dose blood samples will also be collected for protein binding measurement. Safety and tolerability will be evaluated from Day -2 through to the post-study follow-up visit.

The Follow-up Safety visit will be performed 7 days after Sativex® dosing (+ 2 days).

The expected maximum duration for study participation (including Screening, Inpatient Period, and Follow-up) for each individual subject is a maximum of 24 days.

Being tested
Sativex
Keywords
Sativex, GW-1000-02, Nabiximols, Pharmacokinetics, Renal Insufficiency, Chronic Kidney Failure
Medical subject headings
Renal Insufficiency, Kidney Diseases, Marijuana Abuse, Kidney Failure, Chronic

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • SativexDrug

    Also called GW-1000-02, Nabiximols, THC/CBD spray

    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.

Study groups in NCT02325024
Study groupRoleWhat they receive
Renally Impaired SubjectsExperimentalTreatment 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.
Receives: Drug: Sativex
Matched subjects with Normal Renal FunctionExperimentalGroup 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).
Receives: Drug: Sativex

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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-∞))

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

  2. 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-∞)

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

  3. 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-∞)

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

  4. 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-∞)

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

Secondary outcomes (13)

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

    The following are presented for THC;

    • Mean terminal-phase elimination half-life (t(1/2))
    • Mean time to maximum (peak) plasma concentration (tmax)
    • Mean apparent clearance of drug from plasma (CL/F)
    • Mean renal clearance (CLr)
    • Mean fraction of the systemically available drug excreted into the urine (F(e,u))

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

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

    The following are presented for 11-OH-THC;

    • Mean t(1/2)
    • Mean tmax
    • Mean CLr
    • Mean F(e,u)

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

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

    The following are presented for CBD;

    • Mean t(1/2)
    • Mean tmax
    • Mean CL/F
    • Mean CLr
    • Mean F(e,u)

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

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

    The following are presented for 7-OH-CBD;

    • Mean t(1/2)
    • Mean tmax
    • Mean CLr
    • Mean F(e,u)

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

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

    The following are presented for THC:

    • Mean unbound maximum (peak) plasma concentration of the drug (Cmax(u))
    • Mean unbound area under the concentration-time curve calculated to the last observable concentration at time t (AUC(0-t(u)))
    • Mean unbound area under the concentration-time curve from time zero to infinity (AUC(0-∞(u)))
    • Mean apparent unbound clearance of drug from plasma (CLu/F)

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

  6. Pharmacokinetic parameters of 11-OH-THC: Cmax(u), AUC(0-t(u)) and AUC(0-∞(u))

    The following are presented for 11-OH-THC:

    • Mean Cmax(u)
    • Mean AUC(0-t(u))
    • Mean AUC(0-∞(u))

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

  7. Pharmacokinetic parameters of CBD: Cmax(u), AUC(0-t(u)), AUC(0-∞(u)) and CLuF

    The following are presented for CBD:

    • Mean Cmax(u)
    • Mean AUC(0-t(u))
    • Mean AUC(0-∞(u))
    • Mean CLu/F

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

  8. Pharmacokinetic parameters of 7-OH-CBD: Cmax(u), AUC(0-t(u)) and AUC(0-∞(u))

    The following are presented for 11-OH-THC:

    • Mean Cmax(u)
    • Mean AUC(0-t(u))
    • Mean AUC(0-∞(u))

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

  9. The incidence of adverse events as a measure of subject safety

    The number of subjects who experienced an adverse event during the study is presented. The time-frame for adverse event reporting was from screening to the follow-up visit.

    Measured: From screening to follow-up (a maximum of 24 days)

  10. The number of subjects with a clinically significant change in physical and oral examination results, relative to pre-treatment baseline

    The number of subjects with a change in physical and oral examination results indicative of an adverse event, relative to the pre-treatment baseline, is presented.

    Measured: From screening to follow-up (a maximum of 24 days)

  11. The number of subjects with a clinically significant change in 12-lead electrocardiogram (ECG) results, relative to pre-treatment baseline

    The number of subjects with a change in ECG results indicative of an adverse event, relative to the pre-treatment baseline, is presented.

    Measured: From screening to follow-up (a maximum of 24 days)

  12. The number of subjects with clinically significant changes in laboratory test parameters, relative to pre-treatment baseline

    The number of subjects with clinically significant changes in serum biochemistry, hematology and urinalysis, relative to the pretreatment baseline, is presented.

    Measured: From screening to follow-up (a maximum of 24 days)

  13. The number of subjects with a clinically significant change in vital signs, relative to pre-treatment baseline

    The number of subjects with a clinically significant change in vital signs (systolic blood pressure, diastolic blood pressure, pulse rate) indicative of an adverse event, relative to the pre-treatment baseline, is presented.

    A clinically significant drop in blood pressure is defined as a 20 mmHg drop in systolic or 10 mmHg drop in diastolic blood pressure associated with a clinical manifestation of postural hypotension after two minutes standing.

    Measured: From screening to follow-up (a maximum of 24 days)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted24 Dec 2014 (estimated)
  2. Study startJan 2016
  3. Primary completionOct 2016 (estimated)
  4. Study completionOct 2016 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Basic science
Allocation
Non-randomised
Intervention model
Single group
Masking
None (open label)
Enrolment
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02325024
Sponsor's protocol ID
GWCP1426
Other IDs
2014-003104-67, 2014
Status last verified
Aug 2016
First submitted
19 Dec 2014
Last updated
11 Aug 2016
Results posted
No
Data monitoring committee
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Sativex in people with Renal Insufficiency and Kidney Disease, run by GW Pharmaceuticals Ltd.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 27 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: withdrawn, as of the sponsor's last update on 11 Aug 2016. Status can change between updates, so confirm with the study contact before making plans.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was withdrawn before enrolling participants, so there are no results.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Pharmacokinetic parameters of THC: Cmax, AUC(0-t) and AUC(0-∞) (time frame: Pre-dose (t=0) and up to 48 hours post-dose). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02325024.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Aug 2016; AzTrials last refreshed its copy on 7 Nov 2026.

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