A Study to Evaluate Buprenorphine Transdermal Patch in Chinese Subjects With Moderate to Severe Chronic Cancer Pain

NCT03967327 | Unknown Phase 3

• 1 other identifier: BUP14-CN-301
• Study Type: interventional
• Target: 194
• Locations: 1 country
• Sites: 1

Brief Summary

This is a randomised, active-controlled, double-blind, double-dummy, parallel group study with BUP TDS 20 mg (release rate 35 µg/h), 30 mg (release rate 52.5 µg/h) and 40 mg (release rate 70 µg/h), and MOR SR 60 mg, 100 mg or 120 mg per day. The study consists of 3 phases: a Pre-randomisation Phase, a Double-blind Phase and a Safety Follow-up Phase. There will be 194 subjects to be randomized, with 97 randomized subjects in each arm to ensure 154 evaluable (per protocol population) subjects in the study.

Conditions

Cancer Pain

Outcome Measures

Primary Outcomes (1)

• Brief Pain Inventory - Short Form (BPI-SF)

  * To demonstrate the therapeutic non-inferiority of buprenorphine transdermal patches (BUP TDS) compared to morphine sulfate sustained-release tablets (MOR SR) for the management of chronic cancer pain as assessed by the average pain over the last 24 hours on the numeric rating scale (NRS, 0-10) using the Brief Pain Inventory - Short Form (BPI-SF) (Cleeland \& Ryan, 1994) * Moderate to severe inadequate pain at Screening visit (average pain over the last 24 hours ≥ 4 on the 0-10 NRS)

  From visit 3 to study completion, as assessed up to 8 weeks

Study Arms (2)

MOR SR

ACTIVE COMPARATOR

This arm includes MOR SR and placebo for BUP TDS, detailed information is as below: Treatment dosage form dosage frequency duration MOR SR Tablet 10,30,60mg q12h 8 weeks Placebo for Patch -- every 3-4 days 8 weeks BUP TDS

Drug: Buprenorphine transdermal patches; Drug: Morphine Sulfate Sustained-Release Tablet

BUP TDS

EXPERIMENTAL

This arm includes BUP TDS and placebo for MOR SR, detailed information is as below: Treatment dosage form dosage frequency duration Placebo for Tablet -- q12h 8 weeks MOR SR BUP TDS Patch 20/30/40mg every 3-4 days 8 weeks

Drug: Buprenorphine transdermal patches; Drug: Morphine Sulfate Sustained-Release Tablet

Interventions

Buprenorphine transdermal patches DRUG

It should be applied to non-irritated, intact skin of the upper outer arm, upper chest, upper back or the side of the chest. The skin should be relatively hairless. If none are available, the hair at the site should be clipped, not shaven.

BUP TDS; MOR SR

Morphine Sulfate Sustained-Release Tablet DRUG

It will be administered orally twice (q12h) daily.

BUP TDS; MOR SR

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female cancer subjects, 18 years of age or older.
• Females less than one year post-menopausal must have a negative serum pregnancy test recorded at the screening visit, be non-lactating, and willing to use adequate and reliable contraception throughout the study. Highly effective (adequate and reliable) methods of birth control are defined as those which result in a low failure rate (i.e. less than 1% per year) when used consistently and correctly such as sterilization, implants, injectables, combined oral contraceptives, some IUDs (intrauterine Device, hormonal), sexual abstinence or vasectomised partner.
• Documented history of moderate to severe, chronic cancer pain that in the investigators' opinion requires around-the-clock opioid therapy in opioid pre-treated subjects and are likely to benefit from chronic opioid therapy through the administration of BUP TDS (20 mg, 30 mg or 40 mg) or MOR SR (60 mg/d, 100 mg/d or 120 mg/d) for the duration of the study. Subjects must be willing to discontinue their routine current opioid analgesic.
• Subjects with inadequate therapeutic effect (inadequate analgesia or tolerability) with previous WHO step II opioids (weak opioids, e.g. tramadol, codeine) or WHO step III opioids (strong opioid) in the range of morphine equivalent dose level of 40 - 100 mg/d.
• Moderate to severe inadequate pain at Screening visit (average pain over the last 24 hours ≥ 4 on the 0-10 NRS)
• Estimated life expectancy ≥ 3 months.
• Eastern Co-operative Group (ECOG) performance status of 0 - 2.
• The antineoplastic therapies are not planned to be changed or added during the study.
• Subjects willing and able to participate in all aspects for the study, including use of transdermal and oral medication, completion of subjective evaluations, attending scheduled clinic visits, completing telephone contacts, understanding and completing subject diary, and compliance with protocol requirements as evidenced by providing written informed consent.
• In the investigators' opinion the subject's pre-study, non-opioid analgesics, and all other concomitant medications, including those medications for the treatment of depression, will remain stable throughout the double-blind phase of the study, and will be continued under the supervision of the investigator.
• Subjects, who are able to read, understand and sign written informed consent prior to study participation and are willing to follow the protocol requirements.

You may not qualify if:

• Any history of hypersensitivity to buprenorphine, morphine, related products, other opioids and other ingredients.
• Subjects who have not received any opioids treatment, including WHO step II and step III opioids, for the treatment of cancer pain.
• Subjects receiving WHO step III opioids with more than 100 mg morphine-equivalent dose per day within the last 8 weeks before the screening visit.
• Subjects with any situation in which opioids are contra-indicated, severe respiratory depression with hypoxia and/or hypercapnia, severe chronic obstructive pulmonary disease, cor pulmonale, severe bronchial asthma, paralytic ileus, elevated carbon dioxide in the blood.
• Evidence of clinically significant cardiovascular, renal, hepatic, or psychiatric disease, as determined by medical history, clinical laboratory tests, Electrocardiogram (ECG) results, and physical examination, that will place the subject at risk upon exposure to the study treatment or that could confound the analysis and/or interpretation of the study results.
• Abnormal aspartate aminotransferase (AST; SGOT), alanine aminotransferase (ALT; SGPT), gamma-glutamyl transferase (GGT) or alkaline phosphatase levels (\> 3 times the upper limit of normal) or an abnormal total bilirubin and/or creatinine level(s) (\> 1.5 times the upper limit of normal), due to moderate to severe hepatic impairment and/or renal impairment, in the investigators' opinion.
• Radiotherapy that, in the investigators' opinion, would influence pain during the study.
• Cyclic chemotherapy in the 2 weeks before the screening visit or planned during the study that has shown in the past to significantly influence pain assessment or safety profile of subjects (e.g. nausea, vomiting, diarrhoea). If subjects are having their first cycle of chemotherapy during the 2 weeks before the screening visit or during the study they should be excluded.
• Subjects with known or suspected unstable brain metastases or spinal cord compression that may require changes in systemic steroid treatment throughout the duration of the study.
• Subjects with uncontrolled seizures.
• Subjects with head injury, other intracranial lesions or a pre-existing increase in intracranial pressure.
• In the investigators' opinion, subjects who are receiving antihistamines, antipsychotics, anti-anxiety agents, hypnotics, phenothiazine or other central nervous system (CNS) depressants that may pose a risk of additional CNS depression with opioid study treatments.
• Subjects with myxoedema, not adequately treated hypothyroidism or Addison's disease.
• Surgery completed 2 months prior to the screening visit, or planned surgery during the study that may have influence on pain during the study or preclude completion of the study.
• Subjects receiving opioid substitution therapy for opioid addiction (e.g. methadone or buprenorphine).

Sponsors & Collaborators

• Mundipharma (China) Pharmaceutical Co. Ltd: lead

Study Sites (1)

The 81st hospital of the people's liberation army

Nanjing, China

RECRUITING

MeSH Terms

Conditions

Cancer Pain

Condition Hierarchy (Ancestors)

Pain; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• Shukui Qin

  The 81st hospital of the people's liberation army

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Guodong Lu

CONTACT

8610-65636856; guodong.lu@mundipharma.com.cn

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 15, 2019
• First Posted: May 30, 2019
• Study Start: April 22, 2019
• Primary Completion: December 20, 2020
• Study Completion: December 31, 2020
• Last Updated: June 11, 2019

Record last verified: 2019-06

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)