A randomized Phase IIa trial evaluating the safety and efficacy of a new centrally acting analgesic in subjects with pain due to diabetic polyneuropathy

Conditions: painful diabetic polyneuropathy
MedDRA version: 9.1Level: LLTClassification code 10012685Term: Diabetic polyneuropathy

Registration Number: EUCTR2008-004794-18-GB

Lead Sponsor: Grünenthal GmbH

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 108

Inclusion Criteria

1. Subjects must already have signed an Informed Consent Form. Subjects willing to participate in DNA research must have signed the separate Informed Consent Form for DNA research (where local regulations permit).
2. Male or female Caucasian or Hispanic subjects aged 18 years to 75 years inclusive.
3. All subjects must have type 1 or type 2 diabetes mellitus, and must have a documented clinical diagnosis of painful DPN with symptoms and signs for at least 3 months, and pain present at the time of Enrollment.
4. The Investigator considers the subject’s blood glucose to be well controlled by a diet, oral hypoglycemics, or insulin for at least 3 months prior to enrolling in the trial. This control should be documented by a concentration of glycosylated hemoglobin (HbA1C) no greater than 11% at the Enrollment Visit.
5. Subjects that have been taking opioid or non opioid analgesic medication for the painful DPN before the Enrollment Visit must be dissatisfied with their current treatment.
6. A daily average pain intensity score of =4 on the 11 point NRS on at least 3 consecutive days without the use of rescue medication within the 5 day Enrollment Pain Intensity Evaluation Period.
7. Male subjects have to use barrier contraception (condom) during sexual intercourse with females, and no sex with females who are pregnant or lactating will be allowed from the time of dosing of GRT6005 hemi-citrate until 1 month after the final Treatment Period.
Sexually active female subjects must be postmenopausal for at least 2 years, surgically sterile, or practicing an effective method of birth control (e.g., prescription oral contraceptives, contraceptive injections, intrauterine device, double-barrier method, contraceptive patch, male partner sterilization) before entry and 1 month after the final Treatment Period.
Women of childbearing potential must have a negative urine ß-human chorionic gonadotropin (ß-hCG) pregnancy test at the Enrollment Visit and at the Baseline Visit.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

Subjects who meet any of the following criteria will be excluded from participating in the trial:
General:
1. Concurrent participation in another trial, or within 3 months of enrollment into this trial.
2. Previous participation in this or other trials with GRT6005.
3. History of alcohol or drug abuse according to the Investigator’s judgment, based on subject history and physical examination.
4. Known or suspected of not being able to comply with the protocol and with the use of the IMP.
5. Female subjects who are pregnant or breastfeeding.
6. Any clinically significant disease that in the Investigator's opinion may affect efficacy or safety assessments or may compromise the subject’s safety during trial participation, such as, e.g., significant pulmonary, gastrointestinal, endocrine, metabolic (with the exception of diabetes mellitus), neurological, psychiatric disorders (resulting in disorientation, memory impairment or inability to report accurately; for instance, schizophrenia, Alzheimer’s disease).
7. Employees of the Investigator or trial site, with direct involvement in the proposed trial or other trials under the direction of that Investigator or trial site, as well as family members of employees or the Investigator.
8. Subjects with impaired hepatic function determined by international normalized ratio of prothrombin time greater than 1.7 and bilirubin greater than 2.0 mg/dL and albumin lower than 2.8 g per dL or impaired hepatic function with alanine aminotransferase (ALT) or aspartate aminotransferase (AST) greater than 3-fold the upper limit of normal (ULN).
9. History of moderate to severe hepatic impairment; chronic hepatitis B or C, presence of active hepatitis B or C within the past 3 months.
10. Subjects with impaired renal function as determined by chronic kidney disease stage higher than 2 (K/DOQI Clinical Practice Guidelines for Chronic Kidney Disease 2002).
11. Any chronic gastrointestinal disease or previous major abdominal surgery (e.g., Billroth procedure or enteroanastomosis) that might affect drug absorption, or excretion.
12. Significant cardiac disease (e.g., unstable angina pectoris, angina pectoris Canadian Cardiovascular Society (CCS) Class III IV, acute myocardial infarction within the last 3 months, cardiac insufficiency New York Heart Association (NYHA) Class III IV).
13. At the Enrollment Visit and the Baseline Visit, electrocardiogram (ECG) with clinically relevant findings, e.g., marked repolarization abnormality (e.g., suspicious or definite congenital long QT syndrome) and/or QT values of: QTcF for females =450 ms, QTcF for males =430 ms, uncorrected QT =500 ms.
14. Any of the following within 1 year: mild/moderate traumatic brain injury, stroke, transient ischemic attack, brain neoplasm. Severe traumatic brain injury within the last 15 years (consisting of 1 or more of the following: brain contusion, intracranial hematoma, either unconsciousness or posttraumatic amnesia lasting more than 24 h) or residual sequelae suggesting transient changes in consciousness. Life long history of seizure disorder or epilepsy.
15. History of malignancy within the past 2 years, with the exception of basal cell carcinoma that has been treated and is no longer present.
16. Subjects unable to discontinue any of the prohibited medications.
17. Subjects whose body weight is lower than 50 kg.
Trial specific
1. Past or pending litigation due to chronic pain or disability.
2. Any scheduled surgery or painful procedure du

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To evaluate the analgesic efficacy of GRT6005 in subjects with moderate to severe pain due to diabetic polyneuropathy;Secondary Objective: To evaluate the safety and tolerability of GRT6005 and to evaluate the relationship between plasma concentration and analgesic efficacy of GRT6005;Primary end point(s): Reduction from Baseline in average daily pain intensity score (over the last 24 h) measured with the 11 point NRS at the final treatment day of each treatment period, in comparison to placebo.<br>On the basis of data from different doses, a dose response relationship will be assessed. When plasma levels are above the lower limit of quantification, the concentration response relationship will be assessed as well.<br>

Secondary Outcome Measures

Name	Time	Method

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