Inhaled Cannabinoids Versus Immediate-release Oral Opioids for the Management of Breakthrough Cancer Pain (REBORN)

Inhaled PPP001 Versus Immediate-release Oral Opioids for the Management of Breakthrough Pain in Cancer Subjects: a Randomized, Open Label, Crossover, Comparison Study

Breakthrough cancer pain (BTcP) is a rapid onset, high intensity and short duration pain episode, which takes place within stable background pain control. It significantly affects the quality of life of patients with cancer and their ability to function normally. Rapid onset opioids and immediate-release oral opioids (e.g. morphine sulfate, hydromorphone, and oxycodone) are the standard treatment for BTcP. Because of the limited availability, high cost, complicated titration and the high risks of overdosing with rapid-onset opioids, most often the preferred choice of treatment is immediate-release oral opioids. However, this approach might not always offer optimal speed for onset of action and duration to match the rapid nature of an episode of BTcP. In order to seek a potential alternative to immediate-release oral opioids, we are proposing to test the onset of action of PPP001 to rapidly alleviate breakthrough pain in patients with cancer. We will also examine the safety and the efficacy on pain intensity of PPP001 within this population.

Study Overview

• Status: Recruiting
• Conditions: Cancer; Breakthrough Cancer Pain
• Intervention / Treatment: Drug: PPP001; Drug: Morphine sulfate or Hydromorphone or Oxycodone

Detailed Description

The study is a randomized, open-label crossover comparison study: This will be a 10-week open-label randomized study to evaluate the effect of inhaled PPP001 as compared to morphine sulfate or hydromorphone or oxycodone to improve for the treatment of BTcP. After proper screening and verified inclusion/exclusion criteria, 20 consecutive subjects will be recruited.

• Study Type: Interventional
• Enrollment (Anticipated): 20
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Tetra Bio Pharma; Phone Number: 438 899 7575

Study Locations

• United States
  • New Jersey
    • Berlin, New Jersey, United States, 08009
      • Recruiting
      • HRI
      • Contact: Mitchell Hassman, MBA

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Written informed consent.
2. Adult male and female subjects at least 18 years of age.
3. Subject agrees to follow the protocol.
4. Confirmed diagnosis of cancer with life expectancy of more than 3 months; Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2.
5. If currently receiving chemotherapy and/or radiotherapy treatment, subjects must be on a stable regimen for at least one month (30 days ± 2 days) prior to screening.
6. Background cancer pain stable (pain <4/10 on numeric rating scale) and adequately controlled with long-acting oral morphine, oxycodone, hydromorphone, hydrocodone, or meperidine.
7. Subject receiving at least 30 mg of oral morphine equivalent daily doses (MEDD) for both background and breakthrough cancer pain.
8. The subject is currently taking chronic treatment with opiod analgesic but still has a clinical diagnosis of breakthrough cancer pain with <3 episodes per day but >3 episodes per week.
9. The subject is using only oral morphine sulfate for breakthrough opioid analgesia.
10. Normal cognitive status according to MiniCog.
11. The subject is able to perform deep inhalations with FEV1 more than 60%.
12. Ability to read and respond to questions in English.

13. A female subject must meet one of the following criteria:

    If of childbearing potential - agrees to use one of the accepted contraceptive regimens from at least 28 days prior to the first drug administration, during the study and for at least 60 days after the last dose.

    If of non-childbearing potential - should be surgically sterile or in a menopausal state

14. A male subject with sexual partners who are pregnant, possibly pregnant, or who could become pregnant must be surgically sterile or agrees to use one of the accepted contraceptive regimens from first drug administration until 3 months after the last drug administration.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: TRIPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: PPP001; Inhaled cannabinoids (PPP001)	Drug: PPP001; Group assigned to PPP001
ACTIVE_COMPARATOR: Morphine sulfate or Hydromorphone or Oxycodone; Oral morphine sulfate or hydromorphone or oxycodone at the previous stabilized dosage	Drug: Morphine sulfate or Hydromorphone or Oxycodone; Group assigned to morphine sulfate or hydromorphone or oxycodone

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time weighted Sum of Pain Intensity Differences from 0 to 30 minutes (SPID30).	SPID30 score after PPP001 administration or immediate-release oral opioids (morphine sulfate or hydromorphone or oxycodone) administration. The SPID30 calculation is based on a 100 mm pain intensity VAS were 0 mm is the minimum and 100 mm the maximum with higher score representing a worse outcome.	change between 0 min (before starting treatment) and 30 minutes after dosing

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
SPID at 10, 15, and 60 minutes	SPID score after PPP001 administration or immediate-release oral opioids (morphine sulfate or hydromorphone or oxycodone) administration. The SPID calculation is based on a 100 mm pain intensity VAS were 0 mm is the minimum and 100 mm the maximum with higher score representing a worse outcome.	10, 15, and 60 minutes after dosing
Pain intensity difference (PID)	PID score after PPP001 administration or immediate-release oral opioids (morphine sulfate or hydromorphone or oxycodone) administration. The PID calculation is based on a 100 mm pain intensity VAS were 0 mm is the minimum and 100 mm the maximum with higher score representing a worse outcome.	5, 10, 15, 30 and 60 minutes after dosing
Pain relief at 5, 10, 15, 30 and 60 minutes	Subjective pain relief evaluated with a self-administered scale. The pain relief is measured with a five-point scale (0 = none to 4 = complete relief) with a higher score representing a better outcome.	5, 10, 15, 30 and 60 minutes after dosing

Collaborators and Investigators

• Sponsor: Tetra Bio-Pharma
• Collaborators: Cognitive Research Corporation
• Investigators: Principal Investigator: Mitchell Hassman, Hassman Research Institute

Study record dates

Study Major Dates

• Study Start (ACTUAL): May 26, 2021
• Primary Completion (ANTICIPATED): March 1, 2022
• Study Completion (ANTICIPATED): April 1, 2022

Study Registration Dates

• First Submitted: May 22, 2018
• First Submitted That Met QC Criteria: June 8, 2018
• First Posted (ACTUAL): June 21, 2018

Study Record Updates

• Last Update Posted (ACTUAL): July 28, 2021
• Last Update Submitted That Met QC Criteria: July 21, 2021
• Last Verified: July 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pain; Neurologic Manifestations; Cancer Pain; Physiological Effects of Drugs; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Analgesics, Opioid; Narcotics; Morphine; Oxycodone; Hydromorphone
• Other Study ID Numbers: PPP001-Ph2-03

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No