Study of D-Methadone in Patients With Chronic Pain

• Sponsor: Memorial Sloan Kettering Cancer Center (Other)
• Overall Status: Completed
• CT.gov ID: NCT00588640
• Collaborator: (none)
• Enrollment: 10
• Location: 1
• Arms: 3
• Duration (Months): 45
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

The purpose of this study is to determine the safest dose of d-methadone that can be given, without causing severe side effects in most patients with chronic pain. Patients are being asked to participate in the Phase I portion of this study.

Condition or Disease	Intervention/Treatment	Phase
Pain; Bladder Cancer; Breast Cancer; CNS Cancer; Colon Cancer; Esophageal Cancer; Pancreatic Cancer; Prostate Cancer; Uterine Cancer; Head and Neck Cancer; Eye Cancer; Otorhinolaryngologic Neoplasms	Drug: d-Methadone; Drug: D-methadone; Drug: placebo	Phase 1/Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 10 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: A Phase I/II Study of D-Methadone in Patients With Chronic Pain
• Study Start Date: Oct 1, 2004
• Actual Primary Completion Date: Jul 1, 2008
• Actual Study Completion Date: Jul 1, 2008

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Phase I, Group This is an open label dose-ranging trial. The first cohort of 8 patients will receive 40mg of d-methadone every 12 hours.	Drug: d-Methadone; 8 subjects to receive 40 mg d-Methadone twice a day
Experimental: Phase II, Group I patients receiving around the clock opioid therapy-No patients were accrued to this group	Drug: D-methadone; After randomization, patients will take the study drug or placebo for 12 days and then they will cross-over to the opposite arm for another 12 days. The study will end on day 24.
Experimental: Phase II, Group II patients not receiving around the clock opioid therapy.No patients were accrued to this group	Drug: placebo; After randomization, patients will take the study drug or placebo for 12 days and then they will cross-over to the opposite arm for another 12 days. The study will end on day 24.

Outcome Measures

Primary Outcome Measures

1. Number Who Reached a Safe Dose [2 years]

   The number of patients who reached a safe and well tolerated dose of d-methadone

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

Phase I and Phase II portions of the study:

• 18 years of age or older

• Chronic pain with average 24 hour intensity rated at least 3 on a verbal numerical scale from 0-10 during the 24 hours prior to study entry.

• Give informed consent to participate in this study.

• Karnofsky Performance Score (KPS) >= to 80

• Negative urine pregnancy test, verified by the study nurse, at study entry (for women of child-bearing potential). Patients must also use a medically approved contraceptive method during the study period.

Phase I only:

• Responsible companion living with patient during study.

Phase II only:

• Group 1 -- Patients must be taking chronic opioid therapy (long acting morphine, long acting oxycodone, transdermal fentanyl) at a stable dose for a minimum of four days. The dose of as needed short acting opioid does not need to be stable.

• Group 2 -- Patients must not be receiving opioids and must have cancer related neuropathic pain secondary to post-chemotherapy peripheral neuropathy, post-radiation and/or post surgical plexopathy, radiculopathy or neuropathy, or post- herpetic neuralgia.

Exclusion Criteria:

Phase I and Phase II:

• Known hypersensitivity to methadone

• Patient taking methadone or with a history of methadone treatment within one month of study enrollment.

• Patient that requires changes in the dose of one of the following medications within 2 weeks of study enrollment:

• Abacavir,

• Benzodiazepines,

• Carbamazepine,

• Efavirenz,

• Fluconazole,

• Fluvoxamine,

• FOS amprenavir,

• Fosphenytoin,

• Naltrexone,

• Nelfinavir,

• Nevirapine,

• Phenytoin,

• Rifampin,

• Rifapentine,

• Risperidone,

• Ritonavir,

• St. John's Wort,

• Zidovudine

• Hepatic function tests (SGOT, alkaline phosphatase, bilirubin) greater than 2 times the upper limit of normal or creatinine greater than 1.4 within 30 days of study entry.

• Neurologic or psychiatric disease sufficient, in the investigator's opinion, to compromise data collection.

• Women who are pregnant or nursing.

• Women of childbearing potential who do not agree to use a medically recognized method of contraception during the study period.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Memorial Sloan Kettering Cancer Center	New York	New York	United States	10065

Sponsors and Collaborators

• Memorial Sloan Kettering Cancer Center

Investigators

• Principal Investigator: Natalie Moryl, MD, Memorial Sloan Kettering Cancer Center

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Memorial Sloan Kettering Cancer Center

Publications

None provided.

• Responsible Party: Memorial Sloan Kettering Cancer Center
• ClinicalTrials.gov Identifier: NCT00588640
• Other Study ID Numbers: 01-017
• First Posted: Jan 8, 2008
• Last Update Posted: Aug 10, 2016
• Last Verified: Jun 1, 2016

• Keywords provided by Memorial Sloan Kettering Cancer Center: Pain; HEENT cancer
• Additional relevant MeSH terms: Uterine Neoplasms; Eye Neoplasms; Otorhinolaryngologic Neoplasms; Chronic Pain; Methadone; D-methadone

Study Results

Participant Flow

Arm/Group Title	Patients Receiving D-methadone 40 mg
Arm/Group Description	Patient Receiving D-methadone 40 mg
Period Title: Overall Study
STARTED	10
COMPLETED	8
NOT COMPLETED	2

Baseline Characteristics

Arm/Group Title	Patients Receiving D-methadone 40 mg
Arm/Group Description	Patient Receiving D-methadone 40 mg
Overall Participants	10
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	6 60%
>=65 years	4 40%
Sex: Female, Male (Count of Participants)
Female	6 60%
Male	4 40%

Outcome Measures

1. Primary Outcome

Title	Number Who Reached a Safe Dose
Description	The number of patients who reached a safe and well tolerated dose of d-methadone
Time Frame	2 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Phase I, Cohort l
Arm/Group Description	oral d-methadone 40 mg d-Methadone: 8 subjects to receive 40 mg d-Methadone twice a day
Measure Participants	8
Number [participants]	8 80%

Adverse Events

Arm/Group Title	Patients Receiving D-methadone 40 mg
Arm/Group Description	Patient Receiving D-methadone 40 mg
All Cause Mortality
	Patients Receiving D-methadone 40 mg
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Patients Receiving D-methadone 40 mg
	Affected / at Risk (%)	# Events
Total	2/9 (22.2%)
General disorders
Pain - Neck	1/9 (11.1%)	1
Pain - Back	1/9 (11.1%)	1
Other (Not Including Serious) Adverse Events
	Patients Receiving D-methadone 40 mg
	Affected / at Risk (%)	# Events
Total	5/9 (55.6%)
Blood and lymphatic system disorders
Glucose, high (hyperglycemia)	1/9 (11.1%)	1
Hemoglobin	1/9 (11.1%)	1
Cardiac disorders
Prolonged QTc interval	3/9 (33.3%)	3
Gastrointestinal disorders
Constipation	1/9 (11.1%)	1
Vomiting	2/9 (22.2%)	2
General disorders
Fatigue (asthenia, lethargy, malaise)	2/9 (22.2%)	2
Nausea	1/9 (11.1%)	1
Pain - Joint	1/9 (11.1%)	1
Pain - Pain NOS	1/9 (11.1%)	1
Sweating (diaphoresis)	1/9 (11.1%)	1
Psychiatric disorders
Mood alteration - Anxiety	1/9 (11.1%)	1
Renal and urinary disorders
Urinary frequency/urgency	1/9 (11.1%)	1
Skin and subcutaneous tissue disorders
Pruritus/itching	1/9 (11.1%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.