A Multicentre, Randomized, Double-Blind, Double Dummy, Crossover Study to Evaluate the Safety and Efficacy of AD 923 (Fentanyl Sublingual) in Comparison to Morphine Sulphate Immediate Release (MSIR) for the Treatment of Breakthrough Pain in Subjects with Malignancies

Phase 3

Conditions: 10027655
Breakthrough cancer pain

Registration Number: NL-OMON32360

Lead Sponsor: i3 Research

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Pending

Sex: Not specified

Target Recruitment: 33

Inclusion Criteria

1. male or female subjects, 18 years of age and older
2. subjects has a malignancy, receiving opioid therapy, and is tolerant to the opioid therapy. the dose of opioid therapy must be stable for at least 7 days prior to screening visit and should not be changed during the study. mimimum dose of opioid therapy should be 60 mg of morphine or morphine equivalent or 50 µg/hour transdermal fentanyl
3. subject has established an optimal stable dose of MSIR for the treatment of BTP (range 10-60 mg per dose) and has been on this dose for at least 3 consecutive days
4. subject has 2-6 episodes of target BTP per day that require treatment. Breakthrough pain is defined as a transitory flare of moderate to severe pain (on a 4-point scale from 1 to 4; mild, moderate, severe, excruciating) that occurs on a background of persistent pain controlled to moderate intensity or less (as defined by the Breakthrough Pain Questionnaire) by th opioid regimen. if a subject has more than 1 type of BTP, or has BTP in more than 1 location, only 1 of the pains will be identified as a ' target' BTP
5. if female, the subject has a negative urine pregnancy test and is not lactating, or has not been of childbearing potential for at least 3 months prior to study drug administration (postmenopausal for at least 2 years, have had a hysterectomy or bilateral tubal ligation, or be proven to be otherwhise incapable of pregnancy. if of childbearing potential, the subject must have been participating one of the following methods of contraception consistently for at least 1 month prior to study entry and agree to continue participating it during the study: hormonal contraceptives, intrauterine device, spermicide and barrier, spouse/partner sterility; or is practicing abstinence and agrees to continue abstinence or to start an acceptable method of contraception from the above list if sexual activity commences
6. subject is able and willing to understand the study and cooperate with all study instructions
7. subject is able and willing to provide written informed consent
8. subject has a Karnofsky score of *60
9. subject has a life expectancy of *3 months
10. subject or his her caregiver has easy, reliable access to a telephone
Additional Inclusion Criteria for the AD 923 Titration and Stabilization Phase
In addition, subjects must meet all of the following criteria prior to entering the AD 923 Titration and Stabilisation Phase
1. subject continues to meet the critera listed above
2. subject has established an optimal stable dose of MSIR for the treatment of BTP (range of 10-60 mg per dose) and has been on this dose for at least 3 consecutive days. optimal dose of MSIR is defined as the dose that provides, in the subject's and investigator's opinion, the best balance between relief and target pain (in particular without requiring rescue medication) and side effect profile; the selected dose should be stable across 3 consecutive days
3. subject is skilled and compliant with completion of the daily diary for at least 3 consecutive days during the Screening and MSIR Baseline Phase
Inclusion Criteria for Randomisation
in addition, subjects must meet all of the following criteria prior to randomisation and entering the Double-blind Crossover Phase
1. subjects continues to meet criteria 'a' through 'j' listed above
2. subject has been on an optimal stable dose of AD 923 for at least 3 days, optimale stable dose i

Exclusion Criteria

1. subject is a female who is pregnant or lactating
2. subject has any respiratory or cardiac condition that, in the opinion of the investigator, may be clinically worsened by opioids
3. subject has an allergy to the AD 923 product or excipients, namely: fentanyl, dehydrated alcohol, menthol, saccharin, and citrate buffer; or to the MSIR product excipients, namely: morphine sulphate, lactose (anhydrous), pregelatinized maize starch, povidone, purified water, magnesium stearate, talc, and tablet coatings
4. subject has any neurological or psychiatric disease that, in the opinion of the investigator, would compromise data collection
5. subject has uncontrolled or rapidly escalating pain
6. subject has a history of alcohol or substance abuse within the last 2 years
7. subject has hepatic dysfunction as shown by liver function tests (i.e., ALT, AST, ALP, or bilirubin) elevated more than 5 times the upper limit of normal
8. subject has renal dysfunction as shown by creatinine elevated more than 1.5 times the upper limit of normal
9. subject has any significant laboratory test results that, in the opinion of the investigator, will compromise subject safety or the conduct of the study
10. subject has uncontrolled infection
11. subject has received treatment with an investigational drug or has participated in a clinical study within 4 weeks of the screening visit
12. subject has had treatment with radiotherapy to a painful site within 14 days prior to study entry or has had any therapy that could alter pain or response to pain medication
13. subject is taking intrathecal or epidural forms of opioids
14. subject is taking any prohibited medications as described in the concomitant medication section
15. subjects has plans to undergo chemotherapy, radiotherapy, or surgery during the treatment period. the exception is that subjects may continue chemotherapy over the study period, provided it is not expected to alter the pain state or response to pain medication

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>AD 923 sublingual<br /><br>safety and efficacy of AD 923 in comparison to MSIR<br /><br>to show the usually rapid relief of pain with AD 923<br /><br>to assess patient tolerability of AD 923<br /><br>physical examination, including vital signs<br /><br>laboratory assessments<br /><br>assessment of mucositis</p><br>

Secondary Outcome Measures