|E.1 Medical condition or disease under investigation
|E.1.1||Medical condition(s) being investigated ||
|diabetic neuropathic pain
|E.1.2 Medical condition or disease under investigation
|E.1.2||Classification code ||10054095
|E.1.2||Term ||Neuropathic pain
|E.1.3||Condition being studied is a rare disease || No
|E.2 Objective of the trial
|E.2.1||Main objective of the trial ||
|To compare the analgesic efficacy and the safety of ABT-894 (6 mg tablets) administered twice daily (BID) to placebo in the treatment of diabetic neuropathic pain (DNP).
|E.2.2||Secondary objectives of the trial ||
|To explore the pharmacokinetic and pharmacogenetic characteristics of ABT-894 in the DNP population.
|E.2.3||Trial contains a sub-study || Yes
|E.2.3.1||Full title, date and version of each sub-study and their related objectives||
|Pharmacogenetics- please refer to Section 5.3.6 'Pharmacogenetic Variables' in Protocol
|E.3||Principal 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 75 years of age (inclusive) at the
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,
● 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
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 is only accepted as a form of
effective contraception when this is in line with the preferred and usual
lifestyle of the subject. Periodic abstinence (e.g., calendar ovulation,
symptothermal, post-ovulation methods) and withdrawal are not acceptable
method of contraception.)
● A vasectomized partner
● Contraceptives (oral, parenteral or transdermal) for 3 consecutive months
prior to study drug administration, or use of an intrauterine device
● Other acceptable methods (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 result of ≤ 11
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.
13. If male, the subject is surgically sterile (vasectomy), is sexually inactive, or is
using a barrier method (condom) of birth control for the duration of the study and
for 7 days following the last dose of study drug.
|E.4||Principal exclusion criteria||
|1. Subject has a history of an allergic reaction or clinically significant sensitivity or
intolerance to acetaminophen or a NNR agonist.
2. 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.
3. Subject has a symptomatic diagnosis of fibromyalgia that requires treatment.
4. 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).
5. Subject has a clinically symptomatic neuropathic pain condition other than DNP.
6. Subject requires treatment with a NSAID for a non-neuropathic pain condition
(e.g., non-elective 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 is permitted.
7. Subject has a functioning implanted medical device (spinal cord stimulator,
intrathecal pump or peripheral nerve stimulator) for the treatment of neuropathic
8. 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
● Major psychiatric disorder including bipolar disorder, schizophrenia or
borderline personality disorder.
● Other psychiatric disorders as determined by the Investigator.
9. Subject has a history of myocardial infarction (MI).
10. Subject has unstable angina.
11. Subject has ventricular arrhythmia requiring anti-arrhythmic therapy.
12. Subject has undergone a cardiac revascularization procedure.
13. Subject has New York Heart Association (NYHA) functional heart failure
classification of Class III or greater.
14. Has stable angina and has had their anti-anginal medication changed or altered
within the last 3 months.
15. Uncontrolled hypertension (HTN) defined as a systolic BP ≥150 and/or a diastolic
blood pressure ≥ 100 at two consecutive visits (Screening and Baseline).
16. Subject has a clinically significant abnormal ECG or (QTc) of > 450 ms at
17. Subject has any clinically significant infection/injury/illness within thirty (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 at Screening with the exception of a positive result for a known prescribed medication.
22. Subject is consuming more than 4 alcoholic drinks per day.
23. Subject's screening laboratory results show the presence of Hepatitis B surface
antigen (HBs Ag), Hepatitis C antibody (HCV Ab), or active Hepatitis A
immunoglobulin M antibody (HAV IgM Ab).
24. Subject has a known or suspected history of Human Immunodeficiency Virus
25. Subject has clinically significant abnormalities in clinical chemistry, hematology,
or urinalysis, including AST or ALT ≥ 1.5 times the upper limit of the reference
range, or a serum creatinine > 2.0 mg/dL.
26. Subject is pregnant and/or breastfeeding or plans to become pregnant as
documented at the Screening or Baseline visits.
27. Subject is largely or wholly incapacitated, bedridden, or confined to a wheelchair
permitting little or no self-care.
28. Consideration by the Investigator, for any reason, that the subject is an unsuitable candidate to receive ABT-894.
29. Subject has received another investigational product within thirty (30) days of the Screening Visit.
30. Subject requires treatment with a prohibited medication during the course of the
31. Current participation in another clinical study.
32. Previous participation in this or any other ABT-894 studies.
33. Subject has a family history of long-QT syndrome or sudden unexplained cardiac
|E.5 End points
|E.5.1||Primary end point(s)||
|The weekly mean of 24-hour average pain score measured by the 11-point Likert Scale and calculated from subject's daily diary.
|E.6 and E.7 Scope of the trial
|E.6||Scope of the trial
|E.6.9||Dose response|| No
|E.7||Trial type and phase
|E.7.1||Human pharmacology (Phase I)|| No
|E.7.1.1||First administration to humans|| Information not present in EudraCT
|E.7.1.2||Bioequivalence study|| Information not present in EudraCT
|E.7.1.3||Other|| Information not present in EudraCT
|E.184.108.40.206||Other trial type description||
|E.7.2||Therapeutic exploratory (Phase II)|| Yes
|E.7.3||Therapeutic confirmatory (Phase III)|| No
|E.7.4||Therapeutic use (Phase IV)|| No
|E.8 Design of the trial
|E.8.1.3||Single blind|| No
|E.8.1.4||Double blind || Yes
|E.8.1.5||Parallel group|| Yes
|E.8.1.6||Cross over || No
|E.8.2|| Comparator of controlled trial
|E.8.2.1||Other medicinal product(s)|| No
|E.8.2.2||Placebo || Yes
The trial involves single site in the Member State concerned
|| Information not present in EudraCT
|E.8.4|| The trial involves multiple sites in the Member State concerned || Yes
|E.8.4.1||Number of sites anticipated in Member State concerned||3
|E.8.5||The trial involves multiple Member States|| Yes
|E.8.5.1||Number of sites anticipated in the EEA||30
|E.8.6 Trial involving sites outside the EEA
|E.8.6.1||Trial being conducted both within and outside the EEA|| Yes
|E.8.6.2||Trial being conducted completely outside of the EEA|| Information not present in EudraCT
|E.8.6.3||If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned||
|E.8.7||Trial has a data monitoring committee|| No
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|The date of the last subject's last scheduled visit or the actual date of follow-up contact, whichever is longer.
|E.8.9 Initial estimate of the duration of the trial
|E.8.9.1||In the Member State concerned years||
|E.8.9.1||In the Member State concerned months||12
|E.8.9.1||In the Member State concerned days||
|E.8.9.2||In all countries concerned by the trial months||14