<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT03005119</url>
  </required_header>
  <id_info>
    <org_study_id>CS-101</org_study_id>
    <nct_id>NCT03005119</nct_id>
  </id_info>
  <brief_title>Evaluation of the Safety, Tolerability, and Efficacy of Orally Administered PTL201 in MS Patients With Spasticity-related Symptoms</brief_title>
  <official_title>A Phase II, Double-blind, Randomized, Placebocontrolled, Parallel-group, Single-center Study to Evaluate the Safety, Tolerability, and Efficacy of Orally Administered PTL201 in Multiple Sclerosis (MS) Patients With Spasticity-related Symptoms</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>PhytoTech Therapeutics, Ltd.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>PhytoTech Therapeutics, Ltd.</source>
  <oversight_info>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      To evaluate the safety and tolerability of oral administration of PTL201 for relief of&#xD;
      spasticity-related symptoms in 70 MS patients and to evaluate the efficacy of oral&#xD;
      administration of PTL201 in relief of spasticity-related symptoms in MS patients. The&#xD;
      pharmacokinetics of PTL201 in comparison to buccally administered Sativex will be evaluated&#xD;
      in sub-study prior to the efficacy study.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The study will be comprised of the following parts:&#xD;
&#xD;
        1. Pharmacokinetics (PK) sub-study:&#xD;
&#xD;
           A 7-day baseline observation period. Randomized cross-over treatments (Sativex, PTL201),&#xD;
           performed at minimum 7-day washout.&#xD;
&#xD;
           Follow up - one week after the last dosing session.&#xD;
&#xD;
        2. Efficacy study:&#xD;
&#xD;
      A 7-day baseline observation period. Single-blind responder phase - 4 weeks. Randomized,&#xD;
      double-blind, placebo-controlled treatment phase - 4 weeks Follow up - two weeks.&#xD;
&#xD;
      Subjects participating in the pharmacokinetic sub-study will be allowed to participate in the&#xD;
      efficacy study and will not be required to repeat the 7-day observation period of the&#xD;
      efficacy study.&#xD;
&#xD;
      Doses will be titrated over a one-week period until reaching maximum tolerated dose (MTD) for&#xD;
      each participant The MTD will be self administered for three weeks thereafter. Participants&#xD;
      demonstrating response to treatment will continue self administering daily PTL201 treatment&#xD;
      or placebo, for an additional four weeks. Participants will keep a daily diary.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Not yet recruiting</last_known_status>
  <start_date type="Anticipated">March 1, 2018</start_date>
  <completion_date type="Anticipated">December 2018</completion_date>
  <primary_completion_date type="Anticipated">December 2018</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Double (Participant, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Incidence of study treatment-related adverse events (AE)</measure>
    <time_frame>10 weeks (70 days) from beginning of treatment to end of follow-up</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in sNRS scores from randomization to end of placebo-controlled treatment phase</measure>
    <time_frame>during the 4 weeks (28 days) placebo-controlled treatment period</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Incidence of all AEs</measure>
    <time_frame>during 10 week treatment plus follow up period</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percent change in walking velocity</measure>
    <time_frame>during 4 weeks placebo-controlled treatment period</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Clinical Global Impression Improvement (CGI-I) assessment using a 7-point scale condition</measure>
    <time_frame>at randomization (day 29) and the end of placebo-controlled treatment phase (day 57)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cadence (steps/min) assessment</measure>
    <time_frame>at baseline (day 1) end of responder phase (day 29) and end of placebo-controlled treatment phase (day 57)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Stride length (cm) assessment</measure>
    <time_frame>at baseline (day 1) end of responder phase (day 29) and end of placebo-controlled treatment phase (day 57)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>pNRS assessment</measure>
    <time_frame>at baseline (day 1) end of responder phase (day 29) and end of placebo-controlled treatment phase (day 57)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Spasm frequency assessment</measure>
    <time_frame>at baseline (day 1) end of responder phase (day 29) and end of placebo-controlled treatment phase (day 57)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Sleep disturbance assessment</measure>
    <time_frame>at baseline (day 1) end of responder phase (day 29) and end of placebo-controlled treatment phase (day 57)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Assessment of clinical gait measures</measure>
    <time_frame>at baseline (day 1) end of responder phase (day 29) and end of placebo-controlled treatment phase (day 57)</time_frame>
    <description>Timed (sec) 25 foot walk test (T25FW)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Assessment of clinical gait measures</measure>
    <time_frame>at baseline (day 1) end of responder phase (day 29) and end of placebo-controlled treatment phase (day 57)</time_frame>
    <description>Timed (sec) up and go test (TUG)</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Combined modified Ashworth score (cMAS) and MS walking scale 12 (MSWS-12) assessments, posturography measure, Selected spatio-temporal parameters of gait</measure>
    <time_frame>at baseline (day 1) end of responder phase (day 29) and end of placebo-controlled treatment phase (day 57)</time_frame>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">70</enrollment>
  <condition>Multiple Sclerosis</condition>
  <arm_group>
    <arm_group_label>PTL201</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Up to 30 mg/day (30 mg THC, 10 mg CBD), recommended to be administered after meals and if required before bed time. Patients will be instructed not to take more than 10 mg (two capsules) at a single dosing session.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>PTL201 and placebo capsules will be identical in appearance</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>PTL201</intervention_name>
    <description>Two piece acid resistance hard capsule filled with seamless gelatin matrix green beads containing tetrahydrocannabinol (THC) and cannabidiol (CBD). Each capsule contain 5 mg THC and 5 mg CBD</description>
    <arm_group_label>PTL201</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo Oral Capsule</intervention_name>
    <description>Placebo seamless gelatin matrix green beads containing excipients only</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Patient (male or female), age 18-65 years&#xD;
&#xD;
          2. Definite diagnosis of MS, according to McDonald 2010 criteria, at least six months&#xD;
             prior to enrollment, with MS associated spasticity for at least 3 months prior to&#xD;
             enrollment&#xD;
&#xD;
               1. Patients suffer from moderate to-severe MS-associated spasticity (≥4 sNRS), with&#xD;
                  no adequate response to traditional antispastic medications&#xD;
&#xD;
               2. EDSS score: 4 ≤ EDSS ≤ 6; functional motor score ≥3.0 Safety, tolerability and&#xD;
                  efficacy of PTL201 in reducing multiple sclerosis-associated spasticity-related&#xD;
                  symptoms&#xD;
&#xD;
               3. Moderate to severe spasticity in at least two districts of upper and/or lower&#xD;
                  limbs&#xD;
&#xD;
          3. Anti-spasticity agent(s) and/or disease-modifying medications maintained at a stable&#xD;
             dose for 30 days prior to and throughout the study&#xD;
&#xD;
          4. Patients able to self-score spasticity&#xD;
&#xD;
          5. Absence of clinical or neuroradiological relapses from at least three months prior to&#xD;
             study entry&#xD;
&#xD;
          6. Willingness and ability to provide written informed consent&#xD;
&#xD;
          7. Willingness and ability to comply with all study requirements&#xD;
&#xD;
          8. Inclusion criteria for placebo-controlled treatment phase:&#xD;
&#xD;
        No major protocol violations were recorded for the patient in the responder phase and at&#xD;
        least 20% improvement in sNRS&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Concomitant disease or disorder with spasticity-like symptoms or that may influence&#xD;
             the subject's level of spasticity, or medical history suggesting that&#xD;
             relapse/remission is likely to recur during the study or expected to influence&#xD;
             spasticity&#xD;
&#xD;
          2. Currently using or used cannabis or cannabinoid-based medications within 30 days of&#xD;
             study entry and is unwilling to abstain from using them for the duration of the study.&#xD;
&#xD;
          3. Concurrent significant psychiatric, renal, hepatic,cardiovascular or convulsive&#xD;
             disorders&#xD;
&#xD;
          4. History or immediate family history of schizophrenia, other psychotic illness, severe&#xD;
             personality disorder, or other significant psychiatric disorder other than depression&#xD;
             related to MS/MS-associated spasticity.&#xD;
&#xD;
          5. Any known or suspected history of substance abuse/dependence disorder (including&#xD;
             opiate abuse),current heavy alcohol consumption, current use of illicit drug, or&#xD;
             current non-prescribed use of any prescription drug.&#xD;
&#xD;
          6. Poorly controlled epilepsy or recurrent seizures (i.e., one or more seizures in the&#xD;
             past year).&#xD;
&#xD;
          7. Known or suspected hypersensitivity to cannabinoids or to any of the excipients of the&#xD;
             study drugs.&#xD;
&#xD;
          8. Myocardial infarction or clinically significant cardiac dysfunction within 12 months&#xD;
             of study entry or a cardiac disorder that, in the opinion of the investigator, would&#xD;
             put the patient at risk of a clinically significant arrhythmia or myocardial&#xD;
             infarction&#xD;
&#xD;
          9. Female patients of child-bearing potential and male patients whose partner is of&#xD;
             childbearing potential, unless willing to ensure that they or their partner use&#xD;
             effective contraception throughout the study and for three months thereafter&#xD;
&#xD;
         10. Female patient who is pregnant, lactating, or planning pregnancy during the course of&#xD;
             the study or within the 3 months thereafter.&#xD;
&#xD;
         11. Any other significant diseases or disorder, which, in the opinion of the investigator,&#xD;
             participation in the study may either put the patient at risk or may influence the&#xD;
             result of the study, or the patient's ability to participate in the study.&#xD;
&#xD;
         12. Travel outside the country planned during the study.&#xD;
&#xD;
         13. Unwilling to abstain from donating blood during the study.&#xD;
&#xD;
         14. Patients previously randomized into a cannabinoid-based clinical trial for MS pain and&#xD;
             spasticity within 6 months of study entry.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_contact>
    <last_name>Hagit Sacks</last_name>
    <phone>+972 3 6449599</phone>
    <email>hsacks@mmjphytotech.com.au</email>
  </overall_contact>
  <location>
    <facility>
      <name>Sheba medical center</name>
      <address>
        <city>Tel Hashomer, Ramat gan</city>
        <country>Israel</country>
      </address>
    </facility>
    <contact>
      <last_name>Anat Achiron, Prof.</last_name>
      <email>Anat.Achiron@sheba.health.gov.il</email>
    </contact>
  </location>
  <location_countries>
    <country>Israel</country>
  </location_countries>
  <verification_date>September 2017</verification_date>
  <study_first_submitted>December 25, 2016</study_first_submitted>
  <study_first_submitted_qc>December 25, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">December 29, 2016</study_first_posted>
  <last_update_submitted>September 26, 2017</last_update_submitted>
  <last_update_submitted_qc>September 26, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">September 28, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Multiple Sclerosis</mesh_term>
    <mesh_term>Sclerosis</mesh_term>
  </condition_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03005119
org study id: CS-101
nct id: NCT03005119
lead sponsor: 
is fda regulated drug: No
is fda regulated device: No
To evaluate the safety and tolerability of oral administration of PTL201 for relief of
      spasticity-related symptoms in 70 MS patients and to evaluate the efficacy of oral
      administration of PTL201 in relief of spasticity-related symptoms in MS patients. The
      pharmacokinetics of PTL201 in comparison to buccally administered Sativex will be evaluated
      in sub-study prior to the efficacy study.
The study will be comprised of the following parts:

        1. Pharmacokinetics (PK) sub-study:

           A 7-day baseline observation period. Randomized cross-over treatments (Sativex, PTL201),
           performed at minimum 7-day washout.

           Follow up - one week after the last dosing session.

        2. Efficacy study:

      A 7-day baseline observation period. Single-blind responder phase - 4 weeks. Randomized,
      double-blind, placebo-controlled treatment phase - 4 weeks Follow up - two weeks.

      Subjects participating in the pharmacokinetic sub-study will be allowed to participate in the
      efficacy study and will not be required to repeat the 7-day observation period of the
      efficacy study.

      Doses will be titrated over a one-week period until reaching maximum tolerated dose (MTD) for
      each participant The MTD will be self administered for three weeks thereafter. Participants
      demonstrating response to treatment will continue self administering daily PTL201 treatment
      or placebo, for an additional four weeks. Participants will keep a daily diary.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Double (Participant, Investigator)
measure: Incidence of study treatment-related adverse events (AE)
time frame: 10 weeks (70 days) from beginning of treatment to end of follow-up
measure: Change in sNRS scores from randomization to end of placebo-controlled treatment phase
time frame: during the 4 weeks (28 days) placebo-controlled treatment period
measure: Incidence of all AEs
time frame: during 10 week treatment plus follow up period
measure: Percent change in walking velocity
time frame: during 4 weeks placebo-controlled treatment period
measure: Clinical Global Impression Improvement (CGI-I) assessment using a 7-point scale condition
time frame: at randomization (day 29) and the end of placebo-controlled treatment phase (day 57)
measure: Cadence (steps/min) assessment
time frame: at baseline (day 1) end of responder phase (day 29) and end of placebo-controlled treatment phase (day 57)
measure: Stride length (cm) assessment
time frame: at baseline (day 1) end of responder phase (day 29) and end of placebo-controlled treatment phase (day 57)
measure: pNRS assessment
time frame: at baseline (day 1) end of responder phase (day 29) and end of placebo-controlled treatment phase (day 57)
measure: Spasm frequency assessment
time frame: at baseline (day 1) end of responder phase (day 29) and end of placebo-controlled treatment phase (day 57)
measure: Sleep disturbance assessment
time frame: at baseline (day 1) end of responder phase (day 29) and end of placebo-controlled treatment phase (day 57)
measure: Assessment of clinical gait measures
time frame: at baseline (day 1) end of responder phase (day 29) and end of placebo-controlled treatment phase (day 57)
description: Timed (sec) 25 foot walk test (T25FW)
measure: Assessment of clinical gait measures
time frame: at baseline (day 1) end of responder phase (day 29) and end of placebo-controlled treatment phase (day 57)
description: Timed (sec) up and go test (TUG)
measure: Combined modified Ashworth score (cMAS) and MS walking scale 12 (MSWS-12) assessments, posturography measure, Selected spatio-temporal parameters of gait
time frame: at baseline (day 1) end of responder phase (day 29) and end of placebo-controlled treatment phase (day 57)
arm group label: PTL201
arm group type: Experimental
description: Up to 30 mg/day (30 mg THC, 10 mg CBD), recommended to be administered after meals and if required before bed time. Patients will be instructed not to take more than 10 mg (two capsules) at a single dosing session.
arm group label: Placebo
arm group type: Placebo Comparator
description: PTL201 and placebo capsules will be identical in appearance
intervention type: Drug
intervention name: PTL201
description: Two piece acid resistance hard capsule filled with seamless gelatin matrix green beads containing tetrahydrocannabinol (THC) and cannabidiol (CBD). Each capsule contain 5 mg THC and 5 mg CBD
arm group label: PTL201
intervention type: Drug
intervention name: Placebo Oral Capsule
description: Placebo seamless gelatin matrix green beads containing excipients only
arm group label: Placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: No
last name: Hagit Sacks
phone: +972 3 6449599
email: hsacks@mmjphytotech.com.au
facility: 
contact: 
country: Israel
responsible party type: Sponsor
mesh term: Multiple Sclerosis
mesh term: Sclerosis