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

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.

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.

Eligibility Criteria:
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.