A Global, Multicenter, Randomized, Double-Blind, Placebo-Controlled Study Comparing the Safety and Efficacy of ABT-894, Duloxetine and Placebo in Subjects with Diabetic Neuropathic Pain

• Register: EUCTR
• Last refreshed on: 8 October 2021
• Main ID: EUCTR2007-001139-71-FR
• Date of registration: 24/09/2007
• Prospective Registration: Yes
• Primary sponsor: Abbott GmbH & Co. KG
• Public title: A Global, Multicenter, Randomized, Double-Blind, Placebo-Controlled Study Comparing the Safety and Efficacy of ABT-894, Duloxetine and Placebo in Subjects with Diabetic Neuropathic Pain
• Scientific title: A Global, Multicenter, Randomized, Double-Blind, Placebo-Controlled Study Comparing the Safety and Efficacy of ABT-894, Duloxetine and Placebo in Subjects with Diabetic Neuropathic Pain
• Date of first enrolment: 09/11/2007
• Target sample size: 275
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2007-001139-71
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: yes; Open: no; Single blind: no; Double blind: yes; Parallel group: yes; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: yes; Placebo: yes; Other: no
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

France, Germany, Italy

Key inclusion & exclusion criteria

Inclusion criteria:
1. Subject must voluntarily sign and date an informed consent form, approved by an
Independent Ethics Committee (IEC)/Institutional Review Board (IRB), prior to
the conduct of any study-specific procedures.
2. Subject is male or female between 18 and 70 years of age (inclusive) at the
Screening Visit.
3. The subject must have a score of 3 or greater on the physical assessment portion of the Michigan Neuropathic Screening Instrument at the Screening Visit.
4. At the Baseline Visit the subject must meet the following criteria:
? An average score of 4 or greater on the 24-hour average pain score (11-Point
Likert Scale) collected for approximately 7 days prior to the Baseline Visit,
and
? A compliance rating of no less than 60% on the 24-hour average pain score
(11 Point Likert Scale) collected over approximately 7 days prior to the
Baseline Visit.
5. Subject must have an average of 4 or greater on the BPI average of pain score at
the Baseline Visit.
6. Subjects must be able to adhere to the study visit schedule and all other protocol
requirements, including the completion of daily pain diaries.
7. If female, subject is either not of childbearing potential (defined as
postmenopausal for at least two (2) years or surgically sterile [bilateral tubal
ligation, bilateral oophorectomy or hysterectomy]) or subject is of childbearing
potential and practicing at least one (1) of the following methods of birth control:
? Total abstinence from sexual intercourse (minimum 1 complete menstrual
cycle)
? A vasectomized partner
? Contraceptives (oral, parenteral or transdermal) for 3 consecutive months
prior to study drug administration, or use of an intrauterine device
? Double-barrier method (condoms, sponge, diaphragm or vaginal ring with
spermicidal jellies or creams) for a minimum of 1 complete menstrual cycle.
8. If female, subject must have negative results for pregnancy tests performed:
? On serum sample obtained at the Screening Visit within 21 days prior to
initial study drug administration, and
? Prior to dosing on a urine sample.
9. The subject must have a diagnosis of diabetes mellitus (Type 1 or Type 2) and a
diagnosis of painful distal symmetric diabetic polyneuropathy.
10. Subject's distal symmetric diabetic polyneuropathy must be present for a minimum of six (6) months and should have begun in the feet with relative symmetrical onset.
11. Subject has an HgbA1c = 9. Subjects who have an HgbA1c of 10 or 11 may be
included in the study upon the Investigator's consultation with the Abbott Medical
Monitor.
12. Subject must be willing to washout of all analgesics (except stable doses of
NSAIDs for conditions other than DNP) for at least 5 half-lives of the longest
acting analgesic or 2 days whichever is longer and be willing to remain off of
medication during the 7 days prior to 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:
1. In the opinion of the Investigator, the subject has failed previous treatment with
duloxetine for DNP.
2. Subject has a diagnosis of narrow-angle glaucoma.
3. Subject has a history of an allergic reaction or clinically significant sensitivity or
intolerance to duloxetine, acetaminophen, or any other NNR agonist.
4. Subject has a medical condition or illness, which is not well controlled that would,
in the opinion of the Investigator, preclude study participation or interfere with the
assessment of pain and other symptoms of DNP.
5. Subject has a symptomatic diagnosis of fibromyalgia that requires treatment.
Subjects who have a diagnosis of fibromyalgia, but do not require treatment, may
be included in the study upon the investigator's consultation with the Abbott
Medical Monitor.
6. Subject is currently receiving analgesics for conditions other than DNP, except for
stable doses of NSAIDs for a non-neuropathic pain condition (e.g. Osteoarthritis).
7. Subject has a clinically symptomatic neuropathic pain condition other than DNP.
8. Subject requires treatment with a NSAID for a non-neuropathic pain condition
(e.g., non-selective or COX-2 inhibitors) at a dose that has not been stable for at
least 30 days. If the subject is on a stable dose of NSAIDs (> 30 days), inclusion
into the study may be permitted upon discussion with the Abbott Medical Monitor.
9. Subject has a functioning implanted medical device (spinal cord stimulator,
intrathecal pump or peripheral nerve stimulator) for the treatment of neuropathic
pain.
10. Subject has a history of:
? Seizures, including those requiring treatment with anticonvulsant. Febrile
seizures will be permitted at the discretion of the Investigator.
? Major depressive episode within the past two (2) years (as defined by
DSMV IV). Treated major depressive disorder within the past two years may
be included upon the Investigator's consultation with the Abbott Medical
Monitor.
? Major psychiatric disorder including bipolar disorder, schizophrenia or borderline personality disorder.
? Other psychiatric disorders as determined by the Investigator.
11. Subject has a history of myocardial infarction (MI) within six (6) months of the
Screening Visit.
12. Subject has unstable angina.
13. Subject has ventricular arrhythmia requiring anti-arrhythmic therapy.
14. Subject has undergone a cardiac revascularization procedure within 30 days of
Screening.
15. Subject has uncontrolled hypertension (HTN) defined as a systolic blood pressure
(BP) = 160 and/or a diastolic blood pressure (BP) = 100 at Screening and/or
Baseline.
16. Subject has a clinically significant abnormal ECG at Screening.
17. Subject has any clinically significant infection/injury/illness within 30 days prior
to the Screening Visit.
18. Subject has a newly diagnosed clinically significant medical condition that
requires therapeutic intervention (within thirty (30) days prior to the Screening
Visit) or unstable medical condition that significantly impacts health.
19. Subject has an active malignancy of any type or has been diagnosed with or treated for cancer within the past 5 years. Subjects with basal cell carcinoma of the skin that has been successfully treated will be allowed to participate.
20. Subject has an active substance abuse or history of chronic substance abuse within the past year, or prior chronic substance abuse judged likely, by the Investigator, to recur during the study period.
21. Subject has a positive result for drugs of abuse a

Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

diabetic neuropathic pain
MedDRA version: 9.1 Level: LLT Classification code 10054095 Term: Neuropathic pain

Intervention(s)

Product Name: ABT-894
Product Code: ABT-894
Pharmaceutical Form: Capsule, hard
CAS Number: 876170-44-4
Current Sponsor code: ABT-894, A-422894.112
Other descriptive name: 3-(5,6-dichloro-pyridin-3-yl)-1(S),5 (S)-3,6-diazabicyclo[3.2.0]heptane benzenesulfonate
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 1-
CAS Number: 876170-44-4
Current Sponsor code: ABT-894, A-422894.112
Other descriptive name: 3-(5,6-dichloro-pyridin-3-yl)-1(S),5 (S)-3,6-diazabicyclo[3.2.0]heptane benzenesulfonate
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 2-
CAS Number: 876170-44-4
Current Sponsor code: ABT-894, A-422894.112
Other descriptive name: 3-(5,6-dichloro-pyridin-3-yl)-1(S),5 (S)-3,6-diazabicyclo[3.2.0]heptane benzenesulfonate
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 4-
Pharmaceutical form of the placebo: Capsule, hard
Route of administration of the placebo: Oral use

Trade Name: Cymbalta
Pharmaceutical Form: Capsule, hard
CAS Number: 136434-34-9
Current Sponsor code: duloxetine hydrochloride
Other descriptive name: (+)-(S)-N -methyl-g-(1-naphthyloxy)-2-thiophenepropylamine hydrochloride
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 60-
Pharmaceutical form of the placebo: Capsule, hard
Route of administration of the placebo: Oral use

Primary Outcome(s)

Primary end point(s): The weekly mean of 24-hour average pain score measured by the 11-point Likert Scale as calculated from the subject's diary.

Main Objective: To compare the analgesic efficacy and the safety of ABT-894 (1 mg, 2 mg, or 4 mg capsules) administered twice daily (BID) to placebo in the treatment of diabetic neuropathic pain (DNP). Duloxetine 60 mg administered once daily (QD) will be assessed for assay sensitivity.

Secondary Objective: To explore the pharmacokinetic and pharmacogenetic characteristics of ABT-894 in the Diabetic Neuropathic Pain population.

Secondary ID(s)

M06-850

Ethics review

Status: Approved
Approval date: 09/11/2007
Contact:

Results

• Results available: Yes
• Date Posted: 16/06/2016
• Date Completed: 07/10/2008
• URL: https://www.clinicaltrialsregister.eu/ctr-search/trial/2007-001139-71/results