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    The EU Clinical Trials Register currently displays   41472   clinical trials with a EudraCT protocol, of which   6816   are clinical trials conducted with subjects less than 18 years old.
    The register also displays information on   18700   older paediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006).


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    Summary
    EudraCT Number:2008-006891-31
    Sponsor's Protocol Code Number:RAA/2008/013
    National Competent Authority:UK - MHRA
    Clinical Trial Type:EEA CTA
    Trial Status:Completed
    Date on which this record was first entered in the EudraCT database:2010-07-28
    Trial results View results
    Index
    A. PROTOCOL INFORMATION
    B. SPONSOR INFORMATION
    C. APPLICANT IDENTIFICATION
    D. IMP IDENTIFICATION
    D.8 INFORMATION ON PLACEBO
    E. GENERAL INFORMATION ON THE TRIAL
    F. POPULATION OF TRIAL SUBJECTS
    G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
    N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
    P. END OF TRIAL
    Expand All   Collapse All
    A. Protocol Information
    A.1Member State ConcernedUK - MHRA
    A.2EudraCT number2008-006891-31
    A.3Full title of the trial
    A randomised placebo-controlled trial of Lithium carbonate in Amyotrophic Lateral Sclerosis (LiCALS)
    A.3.2Name or abbreviated title of the trial where available
    LiCALS
    A.4.1Sponsor's protocol code numberRAA/2008/013
    A.7Trial is part of a Paediatric Investigation Plan Information not present in EudraCT
    A.8EMA Decision number of Paediatric Investigation Plan
    B. Sponsor Information
    B.Sponsor: 1
    B.1.1Name of SponsorKing's College London
    B.1.3.4CountryUnited Kingdom
    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 support
    B.4.2Country
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisation
    B.5.2Functional name of contact point
    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 Lithium Apogepha
    D.2.1.1.2Name of the Marketing Authorisation holderAPOGEPHA Arzneimittel GmbH
    D.2.1.2Country which granted the Marketing AuthorisationGermany
    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.3.1Product nameLithium Carbonate
    D.3.4Pharmaceutical form Tablet
    D.3.4.1Specific paediatric formulation Information not present in EudraCT
    D.3.7Routes of administration for this IMPOral use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.9.1CAS number 554132
    D.3.9.3Other descriptive nameLITHIUM CARBONATE
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typerange
    D.3.10.3Concentration number295.00 to 885.00
    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) Information not present in EudraCT
    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 Information not present in EudraCT
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) Information not present in EudraCT
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product Information not present in EudraCT
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy Information not present in EudraCT
    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 Information not present in EudraCT
    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.IMP: 2
    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 Lithium Carbonate
    D.2.1.1.2Name of the Marketing Authorisation holdervarious
    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.3.1Product nameLithium Carbonate
    D.3.4Pharmaceutical form Tablet
    D.3.4.1Specific paediatric formulation Information not present in EudraCT
    D.3.7Routes of administration for this IMPOral use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.9.1CAS number 554-13-2
    D.3.9.3Other descriptive nameLITHIUM CARBONATE
    D.3.10 Strength
    D.3.10.1Concentration unit Other
    D.3.10.2Concentration typenot less then
    D.3.10.3Concentration number1 tablet
    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) Information not present in EudraCT
    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 Information not present in EudraCT
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) Information not present in EudraCT
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product Information not present in EudraCT
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy Information not present in EudraCT
    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 Information not present in EudraCT
    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.IMP: 3
    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 Lithium Citrate
    D.2.1.1.2Name of the Marketing Authorisation holdervarious
    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.3.1Product nameLithium Citrate
    D.3.4Pharmaceutical form Oral liquid
    D.3.4.1Specific paediatric formulation Information not present in EudraCT
    D.3.7Routes of administration for this IMPOral use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.9.1CAS number 919164
    D.3.9.3Other descriptive nameLITHIUM CITRATE
    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) Information not present in EudraCT
    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 Information not present in EudraCT
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) Information not present in EudraCT
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product Information not present in EudraCT
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy Information not present in EudraCT
    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 Information not present in EudraCT
    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 Information not present in EudraCT
    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
    Amyotrophic Lateral Sclerosis (ALS)
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 9.1
    E.1.2Level LLT
    E.1.2Classification code 10002026
    E.1.2Term Amyotrophic lateral sclerosis
    E.1.3Condition being studied is a rare disease Yes
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    To assess whether lithium carbonate, in doses achieving blood levels of 0.4-0.8mmols/L, significantly prolongs survival in ALS over 18 months, without clinically significant safety toxicity.
    E.2.2Secondary objectives of the trial
    To assess whether treatment with lithium carbonate slows the rate of functional deterioration over 18 months.
    To assess whether treatment with lithium carbonate affects quality of life or mental state in ALS patients.
    E.2.3Trial contains a sub-study Yes
    E.2.3.1Full title, date and version of each sub-study and their related objectives
    Open Label Extension (as detailed in LiCALS protocol version 7 dated 2nd August 2010)

    Surviving blinded participants who have completed their month 18 visit and who have been on continuous trial medications will be asked whether they would like to participant in an open label extension. Participants must meet the inclusion/ exclusion criteria detailed below.
    The number of patients to be recruited at each of the centres will be based on the number of participants recruited to the double blind section of the study.

    Objective
    • To obtain further evidence of the safety of lithium carbonate (LiCO3), in doses achieving blood levels of 0.4-0.8 mmols/L.

    Outcome
    • Safety monitoring only
    • Survival status

    Inclusion criteria
    1. Participants who have completed week 77 of the LICALS double blind trial.
    2. Age: ≥18 years (inclusive).
    3. In the case of a female with childbearing potential, the patient must not be pregnant or breast-feeding. Women of childbearing potential will have a urine pregnancy test before randomisation; and at each clinic visit. The results of those must be negative. Women of childbearing potential should use adequate contraception.
    4. Capable of understanding the information given and giving fully informed consent prior to any study specific procedures.

    Exclusion criteria
    1. Any laboratory abnormal values considered by the local physician to contraindicate lithium.
    2. Recorded diagnosis or evidence of major psychiatric disorder or clinically evident dementia.
    3. Known allergy or hypersensitivity to lithium, or its excipients.
    4. Likely to be uncooperative or to fail to comply with the trial requirements or to be inaccessible in the event of an emergency.
    5. Subjects with significant haematological, biochemical and autoimmune abnormalities, as judged by the study physician.
    6. If a woman of childbearing potential, unable or unwilling to use effective contraception during the study.
    7. Patients already taking lithium in any form outside the LICALS trial.
    8. Presence of a medical condition contra-indicative to the use of lithium, according to the BNF (http://www.bnf.org/bnf/)
    E.3Principal inclusion criteria
    • Patients with Possible, Laboratory-supported Probable, Probable or Definite ALS according to the revised version of the El Escorial World Federation of Neurology criteria (The ‘Airlie House Statement’: http://www.wfnals.org)
    These criteria are internationally accepted research diagnostic criteria with high specificity and sensitivity. The onset form (bulbar or limb) and disease type (familial or sporadic) will be recorded; source documents will include a full report of an electromyogram (EMG) reported by an experienced neurophysiologist as compatible with ALS.
    • Disease duration ≥6 months and ≤36 calendar months (inclusive), with disease onset defined as date of first muscle weakness, or dysarthria.
    • FVC ≥60% of predicted within 1 month prior to randomisation
    • Age: ≥18 years (inclusive).
    • In the case of a female with childbearing potential, the patient must not be pregnant or breast-feeding. Women of childbearing potential will have a urine pregnancy test before randomisation; and at each clinic visit. The results of those must be negative. Women of childbearing potential should use two barrier methods of contraception.
    • Continuously treated with riluzole for at least 4 weeks prior to screening (28 days inclusive) and stabilised at 100 mg/day (50 mg bid) without significant adverse drug reactions.
    • Capable of understanding the information given and giving fully informed consent prior to any study specific procedures.
    E.4Principal exclusion criteria
    • Participation in another therapeutic study within the preceding 12 weeks or use of other investigational drugs or agents.
    • Tracheostomy, or assisted ventilation of any type during the preceding three months.
    • Existing gastrostomy, unless elective and not currently used for nutritional support or hydration.
    • Any medical condition known to have an association with motor neuron dysfunction which might confound or obscure the diagnosis of ALS.
    • Presence of any concomitant life-threatening disease or any disease or impairment likely to interfere with functional assessment.
    • Confirmed hepatic insufficiency or abnormal liver function (ALT greater than 1.5 the upper limit of the normal range) within one month of randomisation. That blood test may be repeated in the case of initial abnormal results; if the AST and ALT return to normal, the patient may then be included in the study.
    • Renal insufficiency (serum creatinine >200 µmol/L [2.26 mg/dL]) within one month of randomisation. That blood test may be repeated in the case of initial abnormal results; if the AST and ALT return to normal, the patient may then be included in the study.
    • Recorded diagnosis or evidence of major psychiatric disorder or clinically evident dementia.
    • Known allergy or hypersensitivity to lithium, or its excipients.
    • Likely to be uncooperative or to fail to comply with the trial requirements or to be inaccessible in the event of an emergency.
    • Subjects with significant haematological, biochemical and autoimmune abnormalities, as judged by the study physician.
    • If a woman of childbearing potential, unable or unwilling to use effective contraception (two barrier methods) during the study.
    • Patients with active inflammation/infection at screening or Baseline (Day 0). Patients presenting with active inflammation/infection can be reassessed at a later date, and included in the trial if the infection/inflammation has cleared.
    • Patients already taking lithium in any form.
    • Presence of a medical condition contra-indicative to the use of lithium, according to the BNF (http://www.bnf.org/bnf/)
    E.5 End points
    E.5.1Primary end point(s)
    Survival at 18 months from randomisation. The outcome measure therefore is death from any cause.
    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) No
    E.7.3Therapeutic confirmatory (Phase III) No
    E.7.4Therapeutic use (Phase IV) Yes
    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.8.3 The trial involves single site in the Member State concerned No
    E.8.4 The trial involves multiple sites in the Member State concerned Yes
    E.8.4.1Number of sites anticipated in Member State concerned10
    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 Information not present in EudraCT
    E.8.7Trial has a data monitoring committee Yes
    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
    TBC
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years3
    E.8.9.1In the Member State concerned months5
    E.8.9.1In the Member State concerned days0
    E.8.9.2In all countries concerned by the trial years3
    E.8.9.2In all countries concerned by the trial months5
    E.8.9.2In all countries concerned by the trial 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.1.3Elderly (>=65 years) Yes
    F.2 Gender
    F.2.1Female Yes
    F.2.2Male Yes
    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 state220
    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)
    Specified in protocol
    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 Decision2009-01-27
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2009-02-17
    P. End of Trial
    P.End of Trial StatusCompleted
    P.Date of the global end of the trial2012-02-08
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