Summary
EudraCT Number:2019-000702-30
Sponsor's Protocol Code Number:18.021
National Competent Authority:Denmark - DHMA
Clinical Trial Type:EEA CTA
Trial Status:Ongoing
Date on which this record was first entered in the EudraCT database:2019-08-23
Trial results
A. Protocol Information
A.1Member State ConcernedDenmark - DHMA
A.2EudraCT number2019-000702-30
A.3Full title of the trial
Fibromyalgia and Naltrexone: The FINAL study
A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
Fibromyalgia and Naltrexone: The FINAL study
A.3.2Name or abbreviated title of the trial where available
FINAL
A.4.1Sponsor's protocol code number18.021
A.7Trial is part of a Paediatric Investigation Plan No
A.8EMA Decision number of Paediatric Investigation Plan
B. Sponsor Information
B.Sponsor: 1
B.1.1Name of SponsorOdense University Hospital
B.1.3.4CountryDenmark
B.3.1 and B.3.2Status of the sponsorNon-Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1Name of organisation providing supportUniversity of southern Denmark
B.4.2CountryDenmark
B.4.1Name of organisation providing supportRegion of southern Denmark
B.4.2CountryDenmark
B.4.1Name of organisation providing supportThe Danish Rheumatism Association
B.4.2CountryDenmark
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1Name of organisationOdense University Hospital
B.5.2Functional name of contact pointPain centre
B.5.3 Address:
B.5.3.1Street AddressHeden 7-9
B.5.3.2Town/ cityOdense
B.5.3.3Post code5000
B.5.3.4CountryDenmark
B.5.6E-mail[email protected]
D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3IMP RoleTest
D.2 Status of the IMP to be used in the clinical trial
D.2.1IMP to be used in the trial has a marketing authorisation Yes
D.2.1.1.1Trade name Naltrexone
D.2.1.1.2Name of the Marketing Authorisation holderPOA Pharma Scandinavia AB
D.2.1.2Country which granted the Marketing AuthorisationDenmark
D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
D.2.5.1Orphan drug designation number
D.3 Description of the IMP
D.3.4Pharmaceutical form Tablet
D.3.4.1Specific paediatric formulation No
D.3.7Routes of administration for this IMPOral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8INN - Proposed INNNaltrexone hydrochloride
D.3.9.3Other descriptive nameNALTREXONE HYDROCHLORIDE
D.3.9.4EV Substance CodeSUB14629MIG
D.3.10 Strength
D.3.10.1Concentration unit mg milligram(s)
D.3.10.2Concentration typeequal
D.3.10.3Concentration number1.5
D.3.11 The IMP contains an:
D.3.11.1Active substance of chemical origin Yes
D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
The IMP is a:
D.3.11.3Advanced Therapy IMP (ATIMP) No
D.3.11.3.1Somatic cell therapy medicinal product No
D.3.11.3.2Gene therapy medical product No
D.3.11.3.3Tissue Engineered Product No
D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
D.3.11.5Radiopharmaceutical medicinal product No
D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
D.3.11.7Plasma derived medicinal product No
D.3.11.8Extractive medicinal product No
D.3.11.9Recombinant medicinal product No
D.3.11.10Medicinal product containing genetically modified organisms No
D.3.11.11Herbal medicinal product No
D.3.11.12Homeopathic medicinal product No
D.3.11.13Another type of medicinal product No
D.8 Information on Placebo
D.8 Placebo: 1
D.8.1Is a Placebo used in this Trial?Yes
D.8.3Pharmaceutical form of the placeboTablet
D.8.4Route of administration of the placeboOral use
E. General Information on the Trial
E.1 Medical condition or disease under investigation
E.1.1Medical condition(s) being investigated
Fibromyalgia
E.1.1.1Medical condition in easily understood language
Fibromyalgia
E.1.1.2Therapeutic area Diseases [C] - Musculoskeletal Diseases [C05]
MedDRA Classification
E.1.2 Medical condition or disease under investigation
E.1.2Version 20.0
E.1.2Level PT
E.1.2Classification code 10048439
E.1.2Term Fibromyalgia
E.1.2System Organ Class 10028395 - Musculoskeletal and connective tissue disorders
E.1.3Condition being studied is a rare disease No
E.2 Objective of the trial
E.2.1Main objective of the trial
The aim of the trial is to investigate whether treatment with Low dose Naltrexone (LDN) has a superior effect compared with placebo on pain, tenderness and pain sensitivity in female patients with fibromyalgia, evaluated after 12 weeks of treatment.
E.2.2Secondary objectives of the trial
In the study we will also explore secondary aims regarding a possible improvement of early muscular exhaustion and physical fitness, a possible improvement of endogenous pain inhibition and a possible anti-inflammatory effect of LDN in FM patients.
E.2.3Trial contains a sub-study No
E.3Principal inclusion criteria
-Women aged 18-64 years
-Understands and writes Danish
-Fulfills the ACR1990 criteria for fibromyalgia
-A minimum score of 4 in self-reported average pain during the last 7 days on a 0-10 NRS at baseline
-All fertile women have to use safe anti conception
E.4Principal exclusion criteria
-Known allergy against naltrexonehydroclorid
-Pregnancy or breastfeeding. A negative pregnancy test has to be available for all fertile subjects at baseline
-Use of opioids or NSAIDs up to 4 weeks before inclusion in the trial
-Abuse of alcohol or other substances
-Inflammatory rheumatic diseases
-Demyelinating diseases
-Active cancer
-Liver dysfunction (ALAT must not be elevated more than 2-fold over highest reference level)
-Kidney dysfunction (GFR < 59 mL/min)
-Psychotic diseases
-History of suicide attempts
-Suicide ideation – evaluated using PHQ-9 (Item 9 has to be answered “never”)
E.5 End points
E.5.1Primary end point(s)
Average pain during the last 7 days. Change from baseline when assessed after 12 weeks of treatment with LDN or LDN-placebo.
Assessed by asking the participants about the level of average pain during the last 7 days on a 11 point rating scale, ranging from 0-10 (0 = "no pain" and 10 = "unbearable pain") using the first item from the symptom part of the Fibromyalgia Impact Questionnaire Revised.
E.5.1.1Timepoint(s) of evaluation of this end point
After 12 weeks of treatment
E.5.2Secondary end point(s)
Key secondary:

- Global assessment. Change in overall fibromyalgia symptoms from baseline when assessed after 4, 8, and 12 weeks of treatment with LDN or LDN-placebo. Measured by Patient Global Impression of Change on a 1-7 Verbal Rating Scale.

- Impact of fibromyalgia. Change from baseline when assessed after 4, 8, and 12 weeks of treatment with LDN or LDN-placebo. Measured by the Fibromyalgia Impact Questionnaire Revised (FIQR) total score.

- Pain distribution. Change from baseline when assessed after 4, 8, and 12 weeks of treatment with LDN or LDN-placebo.
Assessed by the Widespread Pain Index (WPI) from The American College of Rheumatology 2016 revised criteria for fibromyalgia (ACR-2016).

- Level of pain. Change from baseline when assessed after 4, 8, and 12 weeks of treatment with LDN or LDN-placebo. Assessed by the Fibromyalgia Impact Questionnaire Revised "level of pain" question, asking the participants to rate the average level of pain during the last 7 days on a 11 point rating scale (0 = "no pain" and 10 = "unbearable pain")

- Level of tenderness. Change from baseline when assessed after 4, 8, and 12 weeks of treatment with LDN or LDN-placebo. Assessed by the Fibromyalgia Impact Questionnaire Revised "level of tenderness to touch" question, asking the participants to rate the average level of tenderness to touch during the last 7 days on an 11 point rating scale (0 = "no tenderness" and 10 = "very tender") AND assessed by measurement of pressure pain threshold, using a handheld algometer. Points measured: Right Quadriceps 15 cm proximal of apex patella and left Trapezius 10 cm from acromion.

- Level of fatigue. Change from baseline when assessed after 4, 8, and 12 weeks of treatment with LDN or LDN-placebo.
Assessed by the Fibromyalgia Impact Questionnaire Revised "level of energy" question, asking the participants to rate the average level of energy during the last 7 days on an 11 point rating scale (0 = "lots of energy" and 10 = "no energy").

- Level of sleep disturbance. Change from baseline when assessed after 4, 8, and 12 weeks of treatment with LDN or LDN-placebo. Assessed by the Fibromyalgia Impact Questionnaire Revised "quality of sleep" question asking the participants to rate the average quality of sleep during the last 7 days on an 11 point rating scale (0 = "awoke well rested" and 10 = "awoke very tired").

- Level of depression. Change from baseline when assessed after 4, 8, and 12 weeks of treatment with LDN or LDN-placebo. Assessed by the Fibromyalgia Impact Questionnaire Revised "level of depression" question, asking the participants to rate the average level of depression during the last 7 days on an 11 point rating scale (0 = "no depression" and 10 = "very depressed").

- Level of anxiety. Change from baseline when assessed after 4, 8, and 12 weeks of treatment with LDN or LDN-placebo.
Assessed by the Fibromyalgia Impact Questionnaire Revised "level of anxiety" question, asking the participants to rate the average level of anxiety during the last 7 days on an 11 point rating scale (0 = "not anxious" and 10 = "very anxious").

- Level of cognition. Change from baseline when assessed after 4, 8, and 12 weeks of treatment with LDN or LDN-placebo. Assessed by the Fibromyalgia Impact Questionnaire Revised "level of memory problems" question, asking the participants to rate the average level of memory problems during the last 7 days on an 11 point rating scale (0 = "good memory" and 10 = "very poor memory").

- Level of stiffness. Change from baseline when assessed after 4, 8, and 12 weeks of treatment with LDN or LDN-placebo.
Assessed by the Fibromyalgia Impact Questionnaire Revised "level of stiffness" question, asking the participants to rate the average level of stiffness during the last 7 days on an 11 point rating scale (0 = "no stiffness" and 10 = "severe stiffness").

- Level of physical function. Change from baseline when assessed after 4, 8, and 12 weeks of treatment with LDN or LDN-placebo. Assessed by the physical function domain of Fibromyalgia Impact Questionnaire Revised; asking participants to rate how difficult it is to perform a list of 9 common activities over the previous 7 days on an 11 point scale (0 = "no difficulty" and 10 = "very difficult"). The score is characterized by the sum of the 9 scores (0-90).

- Health-related quality of life. Change from baseline when assessed after 4, 8, and 12 weeks of treatment with LDN or LDN-placebo. Measured by the European Quality of Life 5 Dimensions (EQ-5D) and the European Quality of Life VAS (EQ-VAS). The EQ-5D measures 5 domains including mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Every domain is rated on a 1-5 VRS, a score of 1 indicating no problems, and a score of 5 indicating extreme problems. The EQ-VAS asks the participant to rate their overall health ‘today’ on a 0-100 VAS.





E.5.2.1Timepoint(s) of evaluation of this end point
After 12 weeks of treatment
E.6 and E.7 Scope of the trial
E.6Scope of the trial
E.6.1Diagnosis No
E.6.2Prophylaxis No
E.6.3Therapy Yes
E.6.4Safety Yes
E.6.5Efficacy Yes
E.6.6Pharmacokinetic No
E.6.7Pharmacodynamic No
E.6.8Bioequivalence No
E.6.9Dose response No
E.6.10Pharmacogenetic No
E.6.11Pharmacogenomic No
E.6.12Pharmacoeconomic No
E.6.13Others No
E.7Trial type and phase
E.7.1Human pharmacology (Phase I) No
E.7.1.1First administration to humans No
E.7.1.2Bioequivalence study No
E.7.1.3Other No
E.7.1.3.1Other trial type description
E.7.2Therapeutic exploratory (Phase II) Yes
E.7.3Therapeutic confirmatory (Phase III) No
E.7.4Therapeutic use (Phase IV) No
E.8 Design of the trial
E.8.1Controlled Yes
E.8.1.1Randomised Yes
E.8.1.2Open No
E.8.1.3Single blind No
E.8.1.4Double blind Yes
E.8.1.5Parallel group Yes
E.8.1.6Cross over No
E.8.1.7Other No
E.8.2 Comparator of controlled trial
E.8.2.1Other medicinal product(s) No
E.8.2.2Placebo Yes
E.8.2.3Other No
E.8.2.4Number of treatment arms in the trial2
E.8.3 The trial involves single site in the Member State concerned Yes
E.8.4 The trial involves multiple sites in the Member State concerned No
E.8.5The trial involves multiple Member States No
E.8.6 Trial involving sites outside the EEA
E.8.6.1Trial being conducted both within and outside the EEA No
E.8.6.2Trial being conducted completely outside of the EEA No
E.8.7Trial has a data monitoring committee No
E.8.8 Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial
Last visit - last subject
E.8.9 Initial estimate of the duration of the trial
E.8.9.1In the Member State concerned years2
E.8.9.1In the Member State concerned months5
E.8.9.1In the Member State concerned days0
F. Population of Trial Subjects
F.1 Age Range
F.1.1Trial has subjects under 18 No
F.1.1.1In Utero No
F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) No
F.1.1.3Newborns (0-27 days) No
F.1.1.4Infants and toddlers (28 days-23 months) No
F.1.1.5Children (2-11years) No
F.1.1.6Adolescents (12-17 years) No
F.1.2Adults (18-64 years) Yes
F.1.2.1Number of subjects for this age range: 100
F.1.3Elderly (>=65 years) No
F.1.3.1Number of subjects for this age range: 0
F.2 Gender
F.2.1Female Yes
F.2.2Male No
F.3 Group of trial subjects
F.3.1Healthy volunteers No
F.3.2Patients Yes
F.3.3Specific vulnerable populations Yes
F.3.3.1Women of childbearing potential not using contraception No
F.3.3.2Women of child-bearing potential using contraception Yes
F.3.3.3Pregnant women No
F.3.3.4Nursing women No
F.3.3.5Emergency situation No
F.3.3.6Subjects incapable of giving consent personally No
F.3.3.7Others No
F.4 Planned number of subjects to be included
F.4.1In the member state100
F.5 Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)
Subjects are offered standard treatment for fibromyalgia after end of the trial
G. Investigator Networks to be involved in the Trial
N. Review by the Competent Authority or Ethics Committee in the country concerned
N.Competent Authority Decision Authorised
N.Date of Competent Authority Decision2019-10-25
N.Ethics Committee Opinion of the trial applicationFavourable
N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
N.Date of Ethics Committee Opinion2019-10-30
P. End of Trial
P.End of Trial StatusOngoing