Comparison of Delta-8-THC to Ondansetron in the Prevention of Acute Nausea From Moderately Emetogenic Chemotherapy

• ClinicalTrials.gov Identifier: NCT00285051
• Recruitment Status: Terminated
• First Posted: February 1, 2006
• Last Update Posted: December 23, 2020
• Sponsor: Rafa Laboratories
• Collaborator: Teva Branded Pharmaceutical Products R&D, Inc.
• Information provided by (Responsible Party): Rafa Laboratories

Study Description

Brief Summary:

Patients will be treated for 2 consecutive chemo cycles with the study drug for one and placebo for the other. In addition, patients will receive an injection before the chemo, either ondansetron (if receiving placebo inhalation) or normal saline) if receiving active study drug. They will take study medication for 3 days, 4 times daily and fill out VAS scores before and after doses. Patients will be given rescue medication with each dose.

Condition or disease	Intervention/treatment	Phase
Cancer	Drug: inhaled delta-8-THC 300mcg or 600mcg per dose	Phase 2

Detailed Description:

The study is comparing the use of inhaled delata-8-THC in the prevention of nausea and vomitting in patients being treated with moderately emetogenic chemotherapy, and the patients will continue use for 3 days afterward. Patients will be given rescue medication and will fill out VAS scales for nausea, pain, appetite and dizziness. Patients will be treated for 2 cycles, one cycle receiving active drug (one of 2 doses) and the other placebo. Patients receiving placebo will receive ondansetron injection before chemo and patients receiving active drug will receive a normal saline injection. Patients will take the drug 4 times daily for 3 days. The patients will return to clinic for a visit after 24-48 hours and 4 days. Patients will bring a urine sample to measure metabolite. Patients will be given a diary to monitor dosing and side effects as well as concomitant medication. The study will be conducted in 2 - 3 centers. There will be 108 patients enrolled with 27 in each of 4 groups:

Group 1 cycle 1 - Placebo cycle 2 - 300 mcg of delta-8-THC per dose Group 2 cycle 1 - Placebo cycle 2 - 600 mcg of delta-8-THC per dose Group 3 cycle 1 - 300 mcg of delta-8-THC per doseGroup cycle 2 - Placebo Group 4 cycle 1 - 600 mcg of delta-8-THC per dose cycle 2 - placebo

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 6 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Intervention Model Description: Group 1 cycle 1 - Ondansetron; cycle 2 - 300 mcg of delta-8-THC per dose Group 2 cycle 1 - Ondansetron; cycle 2 - 600 mcg of delta-8-THC per dose Group 3 cycle 1 - 300 mcg of delta-8-THC per dose cycle 2 - Ondansetron Group 4 cycle 1 - 600 mcg of delta-8-THC per dose cycle 2 - Ondansetron
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• Official Title: Study to Compare the Safety and Efficacy of 2 Different Doses of Inhaled D8-THC to Standard Therapy With Ondansetron in the Prevention of Acute Nausea From Moderately Emetogenic Chemotherapy
• Study Start Date: November 2005
• Actual Primary Completion Date: February 2009
• Actual Study Completion Date: February 2009

Arms and Interventions

Arm	Intervention/treatment
Experimental: Group 1; Chemo cycle 1 - IV Ondansetron Chemo cycle 2 - 300 mcg of delta-8-THC per dose	Drug: inhaled delta-8-THC 300mcg or 600mcg per dose; drugs to be used to prevent/treat nausea and/or vomiting due to cancer chemotherapy drug Patients will receive chemotherapy on day 0 and receive study medication, return on day 1or 2 and again on day 4 to return medication. There will be at least 10 days between the last dose of study medication from the first cycle and the first dose for the 2nd cycle.. Patients will receive for each chemotherapy cycle either IV Ondansetron and Placebo inhalation, or IV Placebo and delta-8-THC inhalation. The patients will be randomized to receive one of 2 doses of the THC, either 300mcg or THC or 600mcg of THC; Other Name: IV Ondansetron (comparator)
Experimental: Group 2; Chemo cycle 1 - IV Ondansetron Chemo cycle 2 - 600 mcg of delta-8-THC per dose	Drug: inhaled delta-8-THC 300mcg or 600mcg per dose; drugs to be used to prevent/treat nausea and/or vomiting due to cancer chemotherapy drug Patients will receive chemotherapy on day 0 and receive study medication, return on day 1or 2 and again on day 4 to return medication. There will be at least 10 days between the last dose of study medication from the first cycle and the first dose for the 2nd cycle.. Patients will receive for each chemotherapy cycle either IV Ondansetron and Placebo inhalation, or IV Placebo and delta-8-THC inhalation. The patients will be randomized to receive one of 2 doses of the THC, either 300mcg or THC or 600mcg of THC; Other Name: IV Ondansetron (comparator)
Experimental: Group 3; Chemo cycle 1 - 300 mcg of delta-8-THC per dose, Chemo cycle 2 - IV Ondansetron	Drug: inhaled delta-8-THC 300mcg or 600mcg per dose; drugs to be used to prevent/treat nausea and/or vomiting due to cancer chemotherapy drug Patients will receive chemotherapy on day 0 and receive study medication, return on day 1or 2 and again on day 4 to return medication. There will be at least 10 days between the last dose of study medication from the first cycle and the first dose for the 2nd cycle.. Patients will receive for each chemotherapy cycle either IV Ondansetron and Placebo inhalation, or IV Placebo and delta-8-THC inhalation. The patients will be randomized to receive one of 2 doses of the THC, either 300mcg or THC or 600mcg of THC; Other Name: IV Ondansetron (comparator)
Experimental: Group 4; Chemo cycle 1 - 600 mcg of delta-8-THC per dose Chemo cycle 2 - IV Ondansetron	Drug: inhaled delta-8-THC 300mcg or 600mcg per dose; drugs to be used to prevent/treat nausea and/or vomiting due to cancer chemotherapy drug Patients will receive chemotherapy on day 0 and receive study medication, return on day 1or 2 and again on day 4 to return medication. There will be at least 10 days between the last dose of study medication from the first cycle and the first dose for the 2nd cycle.. Patients will receive for each chemotherapy cycle either IV Ondansetron and Placebo inhalation, or IV Placebo and delta-8-THC inhalation. The patients will be randomized to receive one of 2 doses of the THC, either 300mcg or THC or 600mcg of THC; Other Name: IV Ondansetron (comparator)

Outcome Measures

Primary Outcome Measures :

1. VAS scale for nausea [ Time Frame: Up to 4 days after the patient receives chemotherapy. Measurements taken just before and 2 hours after inhalation morning and evening doses. ]
   subjective measurement of feeling of nausea. Patients to indicate on a horizontal line, how much nausea the patient feels, lower score = less nausea, higher score is more severe. Measurement is made on the line from "none" to "severe" for score.

Secondary Outcome Measures :

1. No. of emesis [ Time Frame: up to the 4 days after patient receives chemotherapy ]
   number of times patient vomits recorded daily after receiving cancer chemotherapy
2. VAS scale for delayed nausea [ Time Frame: Up to the 4 days after patient receives chemotherapy. Measurements taken just before and 2 hours after taking inhalation morning and evening doses. Delayed nausea is nausea that occurs 24 hours or more after receiving cancer chemotherapy. ]
   Subjective measurement of feeling of nausea. Patients to indicate on a horizontal line, lower score = less nausea, higher score is more severe. Measurement is made on the line from "none" to "severe" for score.
3. VAS scale for pain [ Time Frame: Up to the 4 days after the patient takes the study medication after receiving chemotherapy. Measurements taken just before and 2 hours after inhalation morning and evening doses ]
   subjective measurement of feeling of pain at the moment Patients to indicate on a horizontal line, lower score = less pain, higher score is more severe pain. Measurement is made on the line from "none" to "severe" for score.
4. VAS scale for appetite stimulation [ Time Frame: Up to 4 days after patient receives chemotherapy. Measurements are taken just before and 2 hours after taking inhalation morning and evening doses ]
   Patients to indicate on a horizontal line, lower score = less appetite, higher score is more appetite. Measurement is made on the line from "not at all" to "very hungry" for score.
5. VAS scale for dizziness [ Time Frame: before and 2 hours after taking inhalation, morning and evening doses. ]
   subjective measurement of feeling dizzy Patients to indicate on a horizontal line, lower score = less nausea, higher score is more severe. Measurement is made on the line from "none" to "severe" for score.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 85 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion criteria:

• Signed informed consent
• Man or woman between 18 and 85 years of age
• Patients who will be receiving at least 2 more cycles of moderately emetogenic chemotherapy
• Patients who are cognitively intact
• Performance Status of 60% or greater on the Karnofsky Scale
• Negative pregnancy test at screening visit in females of childbearing potential
• Use of appropriate contraceptive methods for females of childbearing potential during treatment (e.g. hormonal contraception, intrauterine device [IUD])

Exclusion Criteria:

• A history of psychiatric illness.
• A history of asthma and any other chronic respiratory illness.
• Subjects who, in the judgment of the investigator, are likely to be non-compliant or uncooperative during the study.
• Serious illnesses such as asthma, diabetes mellitus, active peptic ulcer disease, infection, cardiovascular disease or any other disease which may affect the oucome parameters of this study
• Abnormal liver function tests (ALT, AST or AP > 2.5 x upper normal limit)
• Abnormal renal function (e.g. serum creatinine > 2 x upper normal limit)
• Abnormal pulmonary function test which in the judgment of the investigator is incompatible with inhalation of the study drug
• Known intolerance/hypersensitivity to study drugs (THC, ondansetron or dexamethasone) or drugs of similar chemical structure or pharmacological profile
• History of addiction to alcohol or drugs
• Existing or intended pregnancy or lactation
• Participation in another clinical trial within the last 30 days, simultaneous participation in another clinical trial, or previous participation in this trial

Contacts and Locations

Locations

Israel

Shaare Zedek Medical Center

Jerusalem, Israel

Chaim Sheba Medical Center

Tel Hashomer, Israel

Sponsors and Collaborators

Rafa Laboratories

Teva Branded Pharmaceutical Products R&D, Inc.

Investigators

• Principal Investigator: Nathan Cherny, MD; Shaare Zedek Medical Center, Dept. of Oncology

More Information

• Responsible Party: Rafa Laboratories
• ClinicalTrials.gov Identifier: NCT00285051
• Other Study ID Numbers: Rafa protocol THC002/NVP
• First Posted: February 1, 2006
• Last Update Posted: December 23, 2020
• Last Verified: April 2017

Keywords provided by Rafa Laboratories:

emesis, nausea,

Additional relevant MeSH terms:

Nausea; Signs and Symptoms, Digestive; Ondansetron; Antiemetics; Autonomic Agents; Peripheral Nervous System Agents; Physiological Effects of Drugs; Gastrointestinal Agents; Antipruritics; Dermatologic Agents; Serotonin 5-HT3 Receptor Antagonists; Serotonin Antagonists; Serotonin Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action