Safety and Tolerability of Namisol in the Elderly

NCT01740960 | Completed Phase 1

• 2 other identifiers: GER001-02-032012-001841-42
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

The results of phase I Namisol® study (Klumpers et al. Br J Clin Pharmacol, 2012), implicate that Namisol® may have a favorable PK and PD characteristics and is safe to use in people. However, the study included only young adults with a mean age of 21.4 years. In a previous THC study, subjects age has been associated with treatment response and tolerance of adverse reactions. This association was not supported by Lane et al. and Volicer et al. There is concern about the safety and tolerability of THC in the elderly population. This is because, elderly persons in general have higher risk of adverse drug reactions due to a combination of physiological factors such as decreasing in lean body mass, the reduction of renal and hepatic clearance, and medical comorbidity which can lead to polypharmacy and drug-drug interactions. Therefore, data from the phase I trial cannot be translated directly to an elderly (and likely more vulnerable) population. This makes it important to evaluate the safety and tolerability profiles of different Namisol® doses in the elderly. In our study in progress "Delta-THC in Behavioral Disturbances in Dementia", the Namisol® doses of 0,75 mg and 1,5 mg are, until now, well tolerated by elderly subjects. These doses are, however, very low in comparison with the doses used in phase I study with young adults (5 mg, 6,5 mg and 8 mg). The current study on the safety and tolerability of relatively high doses of Namisol® will help us in the future to provide broad advice on the therapeutic index and safety profile of Namisol® in the elderly population.

Conditions

Drug Safety

Keywords

delta-9-tetrahydrocannabinol; THC; Cannabis

Outcome Measures

Primary Outcomes (1)

• THC adverse effects checklist and self-reporting by the subjects

  Safety and tolerability of Namisol® will be evaluated by assessing the incidence and severity of adverse events on each intervention visit by using a standardized THC adverse effects checklist and self-reporting by the subjects.

  Pre dose, 0h30m, 1h30m and at 2h30m post ingestion

Secondary Outcomes (4)

• Body Sway Test (SwayStar™)

  Pre dose, 0h40m, 0h55m and at 2 hour post ingestion

• Visual analogue scales, subtest "feeling high"

  Pre dose, 0h40m, 0h55m and at 2 hour post ingestion

• Test for Attentional Performance (TAP), subtest alertness

  Pre dose, 0h40m, 0h55m and at 2 hour post ingestion

• Plasma concentrations of THC and its active metabolites 11-OH-THC and THC-COOH

  Pre dose, 0h40m, 0h55m and at 2 hour post ingestion

Study Arms (2)

delta-9-tetrahydrocannabinol

ACTIVE COMPARATOR

Subjects will be randomized to receive 3 doses Namisol® (3 mg, 5 mg, 6,5 mg)

Drug: delta-9-tetrahydrocannabinol

Placebo

PLACEBO COMPARATOR

The control product is placebo, consisting of a tablet with similar appearance and taste of the test product.

Drug: Placebo

Interventions

delta-9-tetrahydrocannabinol DRUG

During the intervention phases, subjects will be randomly allocated to receive 1 of 3 doses Namisol®: 3 mg, 5 mg, 6,5 mg (or placebo) The washout period between the intervention periods will be at least 2 weeks.

Also known as: Namisol, Cannabis, ECP002A

delta-9-tetrahydrocannabinol

Placebo DRUG

On each intervention day the subjects will receive the same amount of drugs in order to insure the blinding of the study

Also known as: The control product is placebo

Placebo

Eligibility Criteria

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

You may qualify if:

• Subject is a healthy old person as established by medical history, physical examination, electrocardiography, results of hematological and biochemical blood tests on screening.
• Age 65 years
• Body mass index between 18.0 and 30 kg m-2
• Subject is able and willing to sign the Informed Consent Form prior to screening evaluations

You may not qualify if:

• Regular cannabis user, defined as: smoking one or more joints per week
• Documented history of sensitivity/idiosyncrasy to cannabis
• Relevant history or presence of severe pulmonary disorders \[e.g. COPD GOLD III or IV\], serious cardiovascular disorders \[e.g. myocardial infarction \< 6 months ago; atrial fibrillation; heart failure NYHA III or IV; severe heart valve disease, orthostatic hypotension defined as systolic drop of 20 mm Hg Safety and Tolerability of Namisol in the Elderly Page 8 Version 2, 10 07 2012 or diastolic drop of 10 mm Hg\], seizures, migraine, psychiatric disorders \[e.g. depression (based on documented history or GDS-30 on screening ≥ 10); mania; psychosis; dementia\], cognitive impairment \[based on documented history or MMSE on screening \< 28, significant renal (GFR \< 30 ml/min) or hepatic disorders \[e.g. cancer, cirrhosis. ALT or AST ≥ twice the upper limit of normal\], diabetes mellitus, coagulation disorders
• Inability to understand the nature and extent of the trial and the procedures required
• Current alcohol abuse or use of more than 2 alcoholic consumptions daily
• History of, or current drug abuse
• Using drugs that are inhibitors of CYP2C9, CYP2C19 and CYP3A4 (see appendix 13.3)
• Participation in a drug trial within 60 days prior to the first intervention day
• Donation of blood within 60 days prior to the first intervention day
• Known lactose intolerance
• Using more than six units of (methyl)xanthine products per day (e.g. coffee, tea, cola, chocolate)
• Smoking more than ten cigarettes per day
• High fall-risk (based on body sway test)

Sponsors & Collaborators

• Radboud University Medical Center: lead

Study Sites (1)

Radboud University Medical Centre, department of Geriatrics

Nijmegen, Gelderland, Netherlands

Location

MeSH Terms

Conditions

Marijuana Abuse

Interventions

Dronabinol; nabiximols

Condition Hierarchy (Ancestors)

Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Cannabinoids; Terpenes; Hydrocarbons; Organic Chemicals

Study Officials

• Marcel Olde Rikkert, prof. dr.

  Radboud University Medical Center Nijmegen

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: November 15, 2012
• First Posted: December 4, 2012
• Study Start: August 1, 2012
• Primary Completion: December 1, 2012
• Study Completion: December 1, 2012
• Last Updated: January 7, 2014

Record last verified: 2012-07

Locations

NL (1)