A Study for the Evaluation of the Safety, Tolerability, and Efficacy of ARX-F02 (Sufentanil NanoTab) Compared to Placebo in the Treatment of Cancer Breakthrough Pain

Study Overview
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Brief Summary
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The purpose of this research study was to evaluate ARX-F02 (Sufentanil NanoTab) versus placebo (sugar pill or inactive substance) in the management of breakthrough pain in cancer patients.

Official Title
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A Multicenter, Randomized, Placebo-Controlled, Crossover Study for the Evaluation of the Safety, Tolerability, and Efficacy of ARX-F02 Compared to Placebo in the Treatment of Cancer Breakthrough Pain

Conditions
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Cancer, Pain

Intervention / Treatment
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* Drug: Sublingual sufentanil NanoTabs™ and placebo NanoTabs™


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients 18 years of age or older with documented clinical history or evidence of a malignancy. Patients must have sufficient pain to require at least the equivalent of 60 mg/day oral morphine, at least 25 mcg/hr transdermal fentanyl, at least 30 mg/day oxycodone, at least 8 mg/day oral hydromorphone for a week or longer. Patient is experiencing 1 - 4 episodes of cancer breakthrough pain per day, on average but not necessarily every day, requiring use of an additional opioid analgesic. Patient has a life expectancy of at least 3 months. Patient must have an Eastern Cooperative Oncology Group (ECOG) performance status rating < 2. Patient must be able to provide reliable documentation of pain intensity, pain relief, use of rescue medication, and global evaluation of treatment personally or with the help of a caregiver. Patient must be able to enter simple commands on a Palm Pilot device, personally or with the help of a caregiver. If patient is female and of childbearing potential she must have a negative urine pregnancy test at screening, and must use medically acceptable methods of birth control. Acceptable methods of birth control include oral or transdermal contraceptives, condom, spermicidal foam, IUD, progestin implant or injection, abstinence, vaginal ring, or sterilization of partner. The reason for non-childbearing potential, such as bilateral tubal ligation, bilateral oophorectomy, hysterectomy, or 1 year or more postmenopausal must be specified in the patient's CRF. Patient must demonstrate the dexterity to handle the single-dose applicator that will be used for placing the NanoTab™ under the tongue. Patient and/or caregiver must demonstrate ability to use the NanoTab™ retrieval tool. There must be a caregiver in the home (or hospice) who will be present for at least 1 hour following each dose during titration. Patient must provide written informed consent. Exclusion Criteria: Patients with uncontrollable or rapidly escalating pain. Patients with a history of psychiatric disease or loss of cognitive function that would prevent patient from providing reliable study documentation. Patients with oral mucositis or stomatitis. Patients with a history of substance abuse within the past year. Patients who are using intrathecal opioids. Patients with underlying pulmonary disease such as sleep apnea or chronic obstructive pulmonary disease characterized by CO2 retention that is deemed clinically significant by the investigator. Patients at risk of significant bradyarrhythmia, in the opinion of the Investigator, due to underlying heart disease. Patients with abnormal chemistry or hematology that are deemed by the investigator to be clinically significant. Abnormalities that are cancer related should be documented. Patients with clinically significant abnormality on the Screening ECG who, in the Investigator's opinion, should not participate in the study. Patients who will be receiving chemotherapy or radiation treatment during the 3-week titration phase or 3-week double-blind phase that, in the Investigator's opinion, may dramatically alter the patient's pain level or response to pain medications. Patients who are taking monoamine oxidase inhibitors (MAOIs), or have taken MAOIs within 14 days prior to enrolling in the study. Patients who have participated in a clinical trial of an investigational drug or device within 30 days of screening visit. Patients who, in the Investigator's opinion, should not participate in the study or may not be capable of following the study schedule or procedures for any reason. Patients who are employees or family members of the Investigator, study center or AcelRx.

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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Titration of sufentanil, the DBL sufentanil & PBO<br>During the Titration Phase, patients titrated to the effective dosage of sublingual sufentanil NanoTab™(20, 30, 40, 60 or 80 mcg). One sublingual sufentanil NanoTab™ was taken as needed for breakthrough pain. During the Double-Blind Phase, patients were then randomized to one of six treatment sequences, each of which included seven active doses of sublingual sufentanil (dosage determined in Titration Phase) and three placebo doses taken in random order. One NanoTab™ was taken as needed for breakthrough pain. | Drug: Sublingual sufentanil NanoTabs™ and placebo NanoTabs™<br>* During the Titration Phase, patients titrated to the dose of sufentanil that provided adequate pain relief without intolerable side effects. Dosages were 20, 30, 40, 60 and 80 mcg. During the Double Blind Phase, patients were randomized to one of six sequences and took 7 doses of sufentanil (dosage determined in the titration phase, and 3 doses of placebo.<br>* Other names: (ARX-F02);|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time-weighted SPID30 | time-weighted SPID30 is the sum of the pain intensity difference (PID) over the 30 minute time period. A pain intensity score of 0 (no pain) to 10 (worse possible pain) is recorded at pre-dose, 10, 15, 30, 45, and 60 minutes post-dose. The pain score at each assessment time through 30 minutes is subtracted from the baseline pain score to provide the total sum score or SPID30. A higher SPID30 is better and indicates a reduction in pain intensity compared to the baseline score. | 30 minutes after dosing | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cancer breakthrough pain