Diabetic Peripheral Neuropathic PainPhase 2NCT00794430
Study of the Safety, Tolerability and Efficacy of V3381 in Patients With Diabetic Peripheral Neuropathic Pain
A Phase 2 study testing V3381 in people with Diabetic Peripheral Neuropathic Pain, run by Vernalis (R&D) Ltd at 31 sites in 4 countries.
Trial summary
Randomised, double-blind, placebo-controlled, parallel group, multicentre study of oral doses of V3381, titrated to effect. A 2-week single-blind run-in period will be followed by a 13 week double-blind titration and maintenance phase. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Diabetic Peripheral Neuropathic Pain
- What is being tested?
- V3381
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 161 participants
- Where
- 31 sitesin 4 countries
- Study dates
- Dec 2008to Dec 2009
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Signed written informed consent
- Male or female aged 18 - 75 (18-65 Czech Republic)
- Diagnosis of diabetes mellitus
- No change in diabetes medications within 4 weeks before screening
- Daily pain attributed to diabetic neuropathy present for at least 6 months immediately prior to study entry
- Presents with pain due to bilateral peripheral neuropathy caused by Type I or Type II diabetes mellitus. Pain must have begun in the feet, with relatively symmetrical onset. Diagnosis confirmed by a score of at least 2 on Section B of the MNSI
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- Judged to be reliable and agree to keep all appointments required by the protocol
- Females should be of non child-bearing potential (i.e. surgically sterilized or >1 year post-menopause). Male subjects who are sexually active with a female partner of child bearing potential must agree to use a barrier method of contraception (eg condom, diaphragm or cervical cap in the female female partner) for the duration of the study (until the follow up visit)
- Additionally, at the baseline visit:
- A mean average pain intensity of at least 4, but less than or equal to 9, on an 11 point Likert NPRS recorded twice daily during the two week placebo run-in; any patient who experiences a >30% decrease in the mean pain score compared to Day -14 during placebo run-in will be excluded, regardless of whether their final score is >4
- Full completion of daily diaries for at least 11 of the days up to Day -1
- Compliance in taking placebo run-in medication twice daily for at least 11 of the days up to Day -1
Who cannot join
- Any clinically significant neurologic disorders (except DPNP)
- Any clinically significant or unstable medical or psychiatric condition that would affect the patient's ability to participate in the study
- Prior renal transplant, current renal dialysis
- Pernicious anemia
- Untreated hypothyroidism
- Amputations or persistent ulceration due to diabetes mellitus
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- Any cardiovascular condition that would contraindicate the use of sympathomimetic amines
- Uncontrolled hypertension
- Known or at high risk of HIV infection
- Any anticipated need for surgery during the study
- Increased risk of seizures (defined as a history of seizure disorder (including alcoholic seizures), family history of seizures and history of head trauma that resulted in loss of consciousness or concussion).
- Any malignancy in the past 2 years (except basal cell carcinoma)
- Pain that cannot be clearly differentiated from, or conditions that interfere with, the assessment of diabetic neuropathic pain
- Use of anticonvulsants, antidepressants (particularly MAO inhibitors), or prescription membrane-stabilizing agents, including topical therapies. Patients currently taking drugs in these classes may have them discontinued prior to entry into the placebo run-in period.
- Use of opioids, especially meperidine (pethidine)
Trial locations and contacts
31 sites in 4 countries.
31 sites in 4 countries
Czechia10 sites
Private Clinic
Brno, Brno, 612 00
Nemocnice Ceske Budejovice
České Budějovice, Ceske Budejovice, 370 87
Private Clinic
Holešov, Holesov, 769 01
Private Clinic
Hranice, Hranice, 753 01
Smetanovy sady
Karlovy Vary, Karlovy Vary, 360 01
Neurologicke oddeleni
Pardubice, Pardubice, 53 002
Private Clinic, Michnova 1622/4
Prague, Prague, 149 00
ResTrial s.r.o.
Prague, Prague, 180 00
Lekarsky dum Ormiga
Zlín, Zlín, 760 01
Diabetology Center
Zlín, 762 75
United Kingdom10 sites
Barnsley Hospital
Barnsley, S75 2EP
MAC UK Neuroscience
Blackpool, FY2 0JH
Addenbrookes Hospital
Cambridge, CB2 0QQ
Colchester Hospital University NHS Foundation Trust
Colchester, CO4 5JL
Royal Infirmary of Edinburgh
Edinburgh, Scotland, EH16 4SA
Ipswich Hospital NHS Trust
Ipswich, Suffolk
Pallium Research Group (Seacroft Hospital)
Leeds, LS14 6UH
St John's Hospital
Livingston, EH54 6PP
Barts and The London NHS Trust
London, EC1A 7BE
Royal Hallamshire Hospital
Sheffield, S10 2JF
United States9 sites
Brigham and Women's Hospital
Boston, Massachusetts, 02115
Radiant Research Inc
Cincinnati, Ohio, 45249
Advanced Biomedical Research of America
Las Vegas, Nevada, 89123
Clinical Trials Inc
Little Rock, Arkansas, 72205
Renstar Inc
Ocala, Florida, 34471
dgd Research
San Antonio, Texas, 78229-4801
Endeavor Clinical Trials
San Antonio, Texas, 78229
Radiant Research Inc
St. Petersburg, Florida, 33781
Neurology & Neuroscience Center of Ohio
Toledo, Ohio, 43623
Canada2 sites
LMC Endocrinology
Thornhill, L4J 8L7
LMC Endocrinology
Toronto, M4R 2G4
About this study
Official title: A Randomised, Double-blind, Placebo-controlled, Multicentre, Parallel Group Study of the Safety, Tolerability and Efficacy of V3381 for up to 13 Weeks in Patients With Diabetic Peripheral Neuropathic Pain (DPNP)
Randomised, double-blind, placebo-controlled, parallel group, multicentre study of oral doses of V3381, titrated to effect. A 2-week single-blind run-in period will be followed by a 13 week double-blind titration and maintenance phase. Doses will be titrated up in 100 mg bid increments every one or two weeks, starting from 100 mg bid. A 2 week follow-up period will conclude patient participation in the study.
Read the detailed description
Patients who provide written informed consent will be screened for entry into the study.
Patients will initially enter a 2-week single-blind run-in phase, during which they will complete an 11 point numerical pain rating scale (NPRS) on their average daily pain; patients with a mean weekly score of >4 and <9 will be allowed to continue in the study to randomisation (unless they have exhibited a >50% decrease in pain score, compared to the Day -14 score, during the run-in).
Patients will be randomised to receive either Placebo (PL) bid (n=75) or V3381 (n=75) and will initially be treated with 100 mg V3381 (or placebo equivalent) twice daily (bid) for one week. Patients will remain on the same study treatment throughout the trial. At the end of one week those patients who adequately tolerated study medication will escalate the dose of V3381 to 200 mg bid on a blinded basis. Patients who do not tolerate 100 mg bid will be withdrawn.
After one week of treatment at the 200 mg bid dose level, those subjects who continue to tolerate adequately 200 mg bid study drug will escalate to 300 mg bid. Subjects who have not tolerated the 200 mg bid dose may revert to the 100 mg bid dose and should remain at this dose level for the remainder of the trial.
After a further 2 weeks of treatment those subjects who continue to tolerate adequately 300 mg bid study drug will escalate to 400 mg bid. Subjects who have not tolerated the 300 mg bid dose may revert to the 200 mg bid dose and should remain at this dose level for the remainder of the trial.
Subjects will then remain on these doses (that is, the dose of V3381 or placebo which they tolerate) for the remaining 9 weeks of the treatment period. In exceptional cases of new intolerability developing, patients may be down-titrated to the next lower dose level.
All patients will be provided with the rescue medication paracetamol (acetaminophen) 650 mg up to four times daily (North America [NA]) or 1000 mg up to three times daily (Europe [EU]) to supplement study drug, should they wish to do so, throughout the study, including the single-blind placebo phase.
Patients will be expected to attend the clinic 9 times (at Screening, Baseline, Week 1, Week 2, Week 4, Week 7, Week 10, Week 13 and Follow-up clinic visits) for safety and efficacy assessments. The safety assessments will include biochemistry, haematology and urinalysis tests, 12 lead electrocardiogram (ECG), vital signs, recording of adverse events, Beck Depression Inventory, review of medication compliance, and of blood glucose control.
The following assessments will also be conducted at each clinic visit during treatment and follow up:
- Modified Brief Pain Inventory for diabetic painful neuropathy (DPN)
- Neuropathic Pain Symptom Inventory
- Patient Clinical Global Impression score
- Investigator Clinical Global Impression score
The Medical Outcomes Survey Short Form-36, Version 2 will be assessed at baseline and Visit 8.
Subjects will complete home diaries on a daily basis on which they will rate average pain using the 11-point Likert NPRS. Sleep interference scores, worst daily pain and use of rescue medication will also be recorded on the daily diaries.
A Steering Committee will be established to provide oversight of the conduct of the trial. A Data Safety Monitoring Board (DSMB) will be convened to periodically review patient safety.
- Conditions
- Diabetic Peripheral Neuropathic Pain
- Being tested
- V3381, Placebo
- Keywords
- Safety, Tolerability, Efficacy, Patients, Diabetic peripheral neuropathic pain.
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
V3381Drug
Also called Indantadol
100 mg capsules, titrated to a maximum of 400 mg bid for 13 weeks
PlaceboDrug
Capsule, bid, for 13 weeks
| Study group | Role | What they receive |
|---|---|---|
| V3381 | Experimental | V3381: titrated from 100 mg bid to maximum 400 mg bid over 4 weeks followed by maintenance phase at highest tolerated dose. Total duration of treatment 13 weeks. Receives: Drug: V3381 |
| Placebo | Placebo comparator | Placebo to match V3381, 100 mg, given according to the same regimen. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Investigate the safety and tolerability of V3381 in patients with diabetic neuropathic pain at doses of up to 400 mg bid
Measured: 17 weeks
Secondary outcomes (1)
Determine the efficacy of V3381 in the treatment of diabetic peripheral neuropathic pain at does of up to 400 mg bid
Measured: 17 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Nov 2008 (estimated)
- Study startDec 2008
- Primary completionDec 2009
- Study completionDec 2009
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Diabetic Peripheral Neuropathic PainStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 161 participants (actual)
Sponsor and investigators
- Lead sponsor
- Vernalis (R&D) Ltd
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Christine Sang, Principal investigator, Brigham and Women's Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00794430
- Sponsor's protocol ID
- V3381-2DPNP-02
- Status last verified
- Jan 2015
- First submitted
- 19 Nov 2008
- Last updated
- 3 Jun 2016
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 3 Jun 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomised, Double-blind, Placebo-controlled, Multicentre, Parallel Group Study of the Safety, Tolerability and Efficacy of V3381 for up to 13 Weeks in Patients With Diabetic Peripheral Neuropathic Pain (DPNP)
- ClinicalTrials.gov ID
- NCT00794430
- Acronym / sponsor ID
- V3381-2DPNP-02
- Conditions
- Diabetic Peripheral Neuropathic Pain
- Keywords
- Safety, Tolerability, Efficacy, Patients, Diabetic peripheral neuropathic pain.
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 161 participants (actual)
- Lead sponsor
- Vernalis (R&D) LtdIndustry (pharma, biotech, devices)
- Study start
- Dec 2008
- Primary completion
- Dec 2009 (actual)
- Study completion
- Dec 2009 (actual)
- First posted
- 20 Nov 2008 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Randomised, double-blind, placebo-controlled, parallel group, multicentre study of oral doses of V3381, titrated to effect. A 2-week single-blind run-in period will be followed by a 13 week double-blind titration and maintenance phase. Doses will be titrated up in 100 mg bid increments every one or two weeks, starting from 100 mg bid. A 2 week follow-up period will conclude patient participation in the study.
Detailed description
Patients who provide written informed consent will be screened for entry into the study.
Patients will initially enter a 2-week single-blind run-in phase, during which they will complete an 11 point numerical pain rating scale (NPRS) on their average daily pain; patients with a mean weekly score of >4 and <9 will be allowed to continue in the study to randomisation (unless they have exhibited a >50% decrease in pain score, compared to the Day -14 score, during the run-in).
Patients will be randomised to receive either Placebo (PL) bid (n=75) or V3381 (n=75) and will initially be treated with 100 mg V3381 (or placebo equivalent) twice daily (bid) for one week. Patients will remain on the same study treatment throughout the trial. At the end of one week those patients who adequately tolerated study medication will escalate the dose of V3381 to 200 mg bid on a blinded basis. Patients who do not tolerate 100 mg bid will be withdrawn.
After one week of treatment at the 200 mg bid dose level, those subjects who continue to tolerate adequately 200 mg bid study drug will escalate to 300 mg bid. Subjects who have not tolerated the 200 mg bid dose may revert to the 100 mg bid dose and should remain at this dose level for the remainder of the trial.
After a further 2 weeks of treatment those subjects who continue to tolerate adequately 300 mg bid study drug will escalate to 400 mg bid. Subjects who have not tolerated the 300 mg bid dose may revert to the 200 mg bid dose and should remain at this dose level for the remainder of the trial.
Subjects will then remain on these doses (that is, the dose of V3381 or placebo which they tolerate) for the remaining 9 weeks of the treatment period. In exceptional cases of new intolerability developing, patients may be down-titrated to the next lower dose level.
All patients will be provided with the rescue medication paracetamol (acetaminophen) 650 mg up to four times daily (North America [NA]) or 1000 mg up to three times daily (Europe [EU]) to supplement study drug, should they wish to do so, throughout the study, including the single-blind placebo phase.
Patients will be expected to attend the clinic 9 times (at Screening, Baseline, Week 1, Week 2, Week 4, Week 7, Week 10, Week 13 and Follow-up clinic visits) for safety and efficacy assessments. The safety assessments will include biochemistry, haematology and urinalysis tests, 12 lead electrocardiogram (ECG), vital signs, recording of adverse events, Beck Depression Inventory, review of medication compliance, and of blood glucose control.
The following assessments will also be conducted at each clinic visit during treatment and follow up:
- Modified Brief Pain Inventory for diabetic painful neuropathy (DPN)
- Neuropathic Pain Symptom Inventory
- Patient Clinical Global Impression score
- Investigator Clinical Global Impression score
The Medical Outcomes Survey Short Form-36, Version 2 will be assessed at baseline and Visit 8.
Subjects will complete home diaries on a daily basis on which they will rate average pain using the 11-point Likert NPRS. Sleep interference scores, worst daily pain and use of rescue medication will also be recorded on the daily diaries.
A Steering Committee will be established to provide oversight of the conduct of the trial. A Data Safety Monitoring Board (DSMB) will be convened to periodically review patient safety.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| V3381 | Experimental | Drug: V3381V3381: titrated from 100 mg bid to maximum 400 mg bid over 4 weeks followed by maintenance phase at highest tolerated dose. Total duration of treatment 13 weeks. |
| Placebo | Placebo comparator | Drug: PlaceboPlacebo to match V3381, 100 mg, given according to the same regimen. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- Signed written informed consent
- Male or female aged 18 - 75 (18-65 Czech Republic)
- Diagnosis of diabetes mellitus
- No change in diabetes medications within 4 weeks before screening
- Daily pain attributed to diabetic neuropathy present for at least 6 months immediately prior to study entry
Key exclusion criteria (15 listed)
- Any clinically significant neurologic disorders (except DPNP)
- Any clinically significant or unstable medical or psychiatric condition that would affect the patient's ability to participate in the study
- Prior renal transplant, current renal dialysis
- Pernicious anemia
- Untreated hypothyroidism
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| V3381Also: Indantadol100 mg capsules, titrated to a maximum of 400 mg bid for 13 weeks | Drug | V3381 |
| PlaceboCapsule, bid, for 13 weeks | Drug | Placebo |
Primary outcome
Investigate the safety and tolerability of V3381 in patients with diabetic neuropathic pain at doses of up to 400 mg bid
Time frame: 17 weeks
1 secondary outcome
Determine the efficacy of V3381 in the treatment of diabetic peripheral neuropathic pain at does of up to 400 mg bid
Time frame: 17 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Jun 2016.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Christine Sang principal investigator
Brigham and Women's Hospital
31 sites in 4 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing V3381 in people with Diabetic Peripheral Neuropathic Pain, run by Vernalis (R&D) Ltd at 31 sites in 4 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 3 Jun 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 31 sites in Czechia, United Kingdom, United States, Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Investigate the safety and tolerability of V3381 in patients with diabetic neuropathic pain at doses of up to 400 mg bid (time frame: 17 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Jun 2016.