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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Cancer, Breakthrough Cancer Pain

Intervention / Treatment
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* Drug: PPP001
* Drug: Morphine sulfate or Hydromorphone or Oxycodone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Written informed consent. Adult male and female subjects at least 18 years of age. Subject agrees to follow the protocol. Confirmed diagnosis of cancer with life expectancy of more than 3 months; Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2. 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. Background cancer pain stable (pain <4/10 on numeric rating scale) and adequately controlled with long-acting oral morphine, oxycodone, hydromorphone, hydrocodone, or meperidine. Subject receiving at least 30 mg of oral morphine equivalent daily doses (MEDD) for both background and breakthrough cancer pain. 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. The subject is using only oral morphine sulfate for breakthrough opioid analgesia. Normal cognitive status according to MiniCog. The subject is able to perform deep inhalations with FEV1 more than 60%. Ability to read and respond to questions in English. 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 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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: PPP001<br>Inhaled cannabinoids (PPP001) | Drug: PPP001<br>* Group assigned to PPP001<br>|
| Active Comparator: Morphine sulfate or Hydromorphone or Oxycodone<br>Oral morphine sulfate or hydromorphone or oxycodone at the previous stabilized dosage | Drug: Morphine sulfate or Hydromorphone or Oxycodone<br>* Group assigned to morphine sulfate or hydromorphone or oxycodone<br>|

What is the study measuring?
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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 |