Primary objective:*Evaluation of the efficacy of ECP002A (*9-THC) on spasticity in patients with MSSecondary objectives:*Evaluation of the efficacy of ECP002A (*9-THC) on pain in patients with MS*Evaluation of the tolerability of ECP002A (*9-THC) in…
ID
Source
Brief title
Condition
- Demyelinating disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Treatment phase: the difference between patients treated with ECP002A (*9-THC)
and patients treated with placebo in the H-reflex/M-wave amplitude ratio as
measured by peripheral nerve stimulation of the tibial nerve
Secondary outcome
Pharmacodynamics:
o severity of spasticity based on a daily diary assessment by the subject on a
0*10 spasticity numerical rating scale (NRS)
o severity of spasticity based on the modified Ashworth scale in lower limb
muscles affected by spasticity
o severity of patient disability based on the Kurtzke expanded disability
status scale (EDSS)
o severity of spasticity: based on the RM-test performed on the muscle of the
lower limb
o severity of spasms based on a daily diary assessment by the subject on a 1*5
numerical spasm frequency scale
o severity of pain based on the short form McGill pain questionnaire (SF-MPQ)
o the patients global impression of change (PGIC) in their disease (seven point
scale)
o the Pittsburgh sleep quality index (PSQI)
o the timed 25 feet (T25FW)
o SDST (attention)
o fatigue severity scale (FSS)
o Guy*s neurological disability scale (GNDS)
o visual analogue scale (VAS) Bowdle (feeling high, internal perception,
external perception)
o VAS Bond & Lader (alertness, mood and calmness)
o body sway
o heart rate
o inflammatory disease markers:MMP-8, MMP-9, TIMP-1, IL-12p40, IL-23, IL-17a,
IL-10, IL-6 and TNF*
Pharmacokinetics:
o steady state Cmax, AUC0-last, tmax
o population pharmacokinetic profile
PK-PD:
o establishment of a PK-PD model for the effect of ECP002A (*9-THC) on
spasticity in MS
Tolerability:
o adverse events
o vital signs
o safety laboratory
Background summary
The endogenous cannabinoid system appears to be tonically active in the control
of spasticity and cannabinoids have been proposed as therapeutic options for
spasticity in multiple sclerosis (MS) because of their ability to reduce the
subjective feeling of spasticity. Cannabinoids have been shown to modulate
motor cortical excitability probably through presynaptic cannabinoid receptors
CB1 that control the release of neurotransmitters from axonal terminals. *9-
tetrahydrocannabinol (*9-THC) is one of the cannabinoids in the Cannabis sativa
plant and a direct agonist of the cannabinoid receptor CB1.
Oral bioavailability of *9-THC is variable and the current formulation is
expected to have superior pharmacokinetic properties to previous formulations,
leading to more stable *9-THC plasma levels without high peaks which will
beneficially influence the occurrence of side effects.
Study objective
Primary objective:
*Evaluation of the efficacy of ECP002A (*9-THC) on spasticity in patients with
MS
Secondary objectives:
*Evaluation of the efficacy of ECP002A (*9-THC) on pain in patients with MS
*Evaluation of the tolerability of ECP002A (*9-THC) in patients with MS
*Establishment of a PK-PD model for the effect of ECP002A (*9-THC) on
spasticity in patients with MS
Study design
*This will be a two-phased study consisting of a dose-finding (PK-PD) phase and
a treatment phase
*I
n the dose-finding phase the effect of an escalating dose of ECP002A (*9-THC)
on spasticity will be determined in a randomized placebo-controlled two-way
cross-over fashion. Patients will visit the outpatient clinic on two occasions
and will receive an escalating dose of ECP002A (*9-THC) or placebo. Spasticity
will be scored objectively and subjectively, as will psychotropic effects of *9-
THC. Plasma levels of ECP002A (*9-THC) will be measured.
*
Based on the pharmacokinetics and pharmacodynamic response of the individual
patient, an individual dosing regimen will be generated.
*In the treatment phase, the individual dose as determined based on the
dose-finding phase will be given in a randomized placebo-controlled two-group,
parallel, trial. The treatment period will be 4 weeks.
*
Treatment arms (in the treatment phase):
o ECP002A (*9-THC) at an individually predetermined dose
o Matching placebo
Intervention
ECP002A (*9-THC)
Study burden and risks
The risk of participation includes the possible side-effects of the study drug
(i.e. tachycardia, feeling high, changed perception of time, disturbance in
attention, drowsiness, nausea) and findings during test (i.e. positive test
result for hepatitis B, hepatitis C or HIV)
Jonkerbosplein 52
Nijmegen 6534 AB
NL
Jonkerbosplein 52
Nijmegen 6534 AB
NL
Listed location countries
Age
Inclusion criteria
1. Subject is legally competent;
2. Subject is eighteen years of age or older;
3. Subject is able to speak, read and understand the local language of the investigational site, is familiar with the procedures of the study, and agrees to participate in the study program by giving oral and written informed consent prior to screening evaluations;
4. Subject has a diagnosis of progressive (primary or secondary) Multiple Sclerosis according to the revised McDonald criteria;
5. Subject has a disease duration of more than 1 year as defined by a diagnosis of MS at least one year prior to inclusion in the trial;
6. Subject has clinically stable disease > 30 days.
Exclusion criteria
1. Baseline Expanded Disability Status Scale (EDSS) score < 4.5 or > 7.5;
2. Subject does not have spasticity in at least one of the lower limbs as defined by an Ashworth score * 2;
3. Subject has a body mass index (BMI) below 18 or above 28.5 kg/m2;
4. Subject has a presence or a significant history of any cardiac or vascular disorder, asthma or other pulmonary disease, major gastrointestinal abnormalities, peptic ulceration, hepatic, psychiatric, haematological (including bleeding disorders), endocrine, renal, or major genitourinary disease or neurological disease other than MS or uses any kind of concomitant medication that - in the opinion of the investigator - may interfere with the study;
5. Subject has a (history of) a significant medical disorder that may pose a risk for the subject or jeopardize the aims of the study, based on medical history, physical examination, ECG and safety laboratory parameters;
6. Subject has a presence or history of clinically significant psychiatric illness in first degree relatives;
7. History of sensitivity / idiosyncrasy to THC, compounds chemically related to these compounds, or excipients which may be employed in the study or to any other drug used in the past;
8. Subject is currently a regular user (including *recreational uses*) of any illicit drugs, except for cannabis, or has (a history of) drug or alcohol abuse (alcohol consumption > 40 grams/day or 4 units/day);
9. Subject smokes more than 10 cigarettes or 2 cigars or 2 pipes per day and/or not able or not willing to refrain from smoking on study days;
10. Subject is a habitual and heavy consumer of caffeinated beverages (more than 6 cups of coffee or equivalent/day) at the time of the study and/or is not able to refrain from use of (methyl) xanthines (e.g. coffee, tea, cola, chocolate) from 12 hours prior to dosing until the end of the study day;
11. Unable/unwilling to refrain from all use of grapefruit from 2 weeks prior to the first dose until the last study day and/or unable/unwilling to refrain from all use of quinine containing products from 2 days prior to the first dose until discharge;
12. Positive alcohol breath test at screening or admission and/or unable/unwilling to refrain from alcohol use from 48 hours before each study day until the last blood sample has been drawn;
13. Positive urine screen at screening for other drugs than THC or benzodiazepines, i.e., cocaine, opioids, MDMA, methamphetamine and amphetamines;
14. Positive urine drug test, including THC prior to first dosing;
15. Positive test result on hepatitis B surface antigen, hepatitis C antibody or HIV antibody test;
16. Participation in an investigational drug study within 90 days prior to the first dose and during the entire study period;
17. Donation of blood/plasma outside limits of Sanquin Blood Supply Foundation guidelines;
18. Premenopausal women not using one of the monophasic oral contraceptives (including Diane-35), who are unable or unwilling to also skip the pill/ring-free week, from the screening until the end of the first study phase and during the second study phase;
19. Pregnant and/or breastfeeding subjects;
20. Clinically significant history of use of CNS medication as judged by the investigator.
21. Unable to stay in the Netherlands for more than four weeks.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2010-022033-28-NL |
| CCMO | NL34443.029.10 |