IV Iron Treatment of Restless Legs Syndrome

Restless Legs Syndrome Clinical Trial

Official title:

A Phase II, Six-week, Randomised, Comparative, Double-blind Study of Intravenous Iron Isomaltoside 1000 Versus Placebo in Subjects With Restless Leg Syndrome With a 3 Month Extension

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT02484768
• Other study ID #: P-RLS-01
• Status: Withdrawn
• Phase: Phase 2
• First received: March 30, 2015
• Last updated: June 25, 2015
• Start date: January 2015
• Est. completion date: February 2015

Study information

• Verified date: June 2015
• Source: Pharmacosmos A/S
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to to establish proof-of-concept for efficacy of iron isomaltoside 1000 in subjects with Restless Legs Syndrome.

The study is a randomised, comparative, double-blind study with a 3 months extension. Subjects with restless leg syndrome (RLS) will be randomised 2:1 to one of the following treat-ment groups:

• Group A (42 subjects): 1000 mg iron isomaltoside 1000

• Group B (21 subjects): Placebo infusion

Furthermore, non-responders, who continue to meet entry requirements, will receive 1000 mg iron isomaltoside 1000 at week 6.

Description:

RLS is a disorder of sensation with a prevalence of around 2-5 % of the population. RLS is extremely responsive to dopaminergic agents, but a second issue is that iron deficiency states may precipitate RLS in as much as 25-30 % of subjects with iron deficiency. RLS appears to be related to deficits in brain iron content and metabolism. Magnetic resonance imaging (MRI) images demonstrate a decrease in substantia nigra and red nucleus iron content. The severity of this decrease in brain iron content is correlated with the severity of symptoms. A number of patients are quite resistant to dietary iron repletion but do resolve symptoms with high doses of intravenous (IV) iron.

For the individual subject, there will be 4 phases to the study which includes teleconferences (TCs) and 2 visits.

The treatment and treatment evaluation is the main study.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: February 2015
• Est. primary completion date: February 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Age = 18 years

2. Diagnosis of RLS based upon the CH-RLSq and HTDI

3. IRLS score = 15 at baseline evaluation when off RLS medications

4. Willingness to participate and signing the informed consent form

Exclusion Criteria:

1. S-ferritin > 300 ng/mL and/or TfS > 50 %

2. Iron overload or disturbances in utilisation of iron (e.g. haemochromatosis and haemo-siderosis)

3. Known hypersensitivity to IV iron or any excipients in the investigational drug prod-ucts

4. Pregnant or nursing women. In order to avoid pregnancy, women of childbearing po-tential have to use adequate contraception (e.g. intrauterine devices, hormonal contra-ceptives, or double barrier method) during the whole study period and 7 days after the last dosing

5. History of active asthma within the last 5 years

6. Decompensated liver cirrhosis or active hepatitis (defined as ASAT or ALAT > 3 times upper limit of normal)

7. Active acute or chronic infections (assessed by clinical judgement supplied with WBC and CRP)

8. Rheumatoid arthritis with symptoms or signs of active inflammation

9. Pregnant or nursing women

10. Previous IV iron treatment for RLS

11. IV iron treatment within 1 year prior to screening

12. Blood transfusion within 4 weeks prior to screening

13. Planned elective surgery during the study

14. Participation in any other interventional study where the study drug has not passed 5 half-lives prior to the screening

15. Any other medical condition that, in the opinion of the Investigator, may cause the subject to be unsuitable for the completion of the study or place the subject at potential risk from being in the study, e.g. history of multiple allergies, a malignancy, uncon-trolled hypertension, unstable ischaemic heart disease, or uncontrolled diabetes melli-tus

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Psychomotor Agitation
• Restless Legs Syndrome
• Syndrome

Intervention

Drug:
• Iron isomaltoside 1000
Intravenous treatment
• Sodium Chloride 0.9%
Intravenous treatment

Locations

Country	Name	City	State
n/a

Sponsors (3)

Lead Sponsor	Collaborator
Pharmacosmos A/S	BioStata, Laboratory Corporation of America

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Type and incidence of adverse drug reactions (ADRs)		from baseline to t = 18 weeks	Yes
Other	Number of adverse events (AEs) of special interest	(i.e. hypersensitivity symptoms such as: urticaria, oedema, bronchospasm, hypotension, cardiorespiratory arrest, syn-cope, unresponsiveness, or loss of consciousness at pre-specified time points in relation to administration of study drug)	from baseline to t = 18 weeks	Yes
Other	Change in haematology parameters, s-sodium, s-potassium, s-calcium, s-phosphate, s-urea, s-creatinine, s-albumin, s-bilirubin, aspartate aminotransferase (ASAT), and ala-nine aminotransferase (ALAT) from baseline to week 6 and month 3		from baseline to t = 18 weeks	Yes
Other	Change in vital signs (heart rate and blood pressure) during drug administration		from baseline to t = 18 weeks	Yes
Other	Clinical significant electrocardiogram (ECG) during drug administration		from baseline to t = 18 weeks	Yes
Primary	To measure the change in RLS symptoms from baseline to week 6 measured by the clinical global impression (CGI) score		6 weeks	No
Secondary	Change in RLS symptoms from baseline to week 4 and month 2 and 3 measured by the CGI score		3 months	No
Secondary	Change in RLS symptoms from baseline to week 4 and 6 and month 2 and 3 measured by the International Restless Legs Scale (IRLS)		from baseline to t = 12 weeks	Yes
Secondary	Time from baseline to start of RLS medication		from baseline to t = 6 weeks	No
Secondary	Time from baseline to start of RLS medication or non-response (CGI = 3 at week 6)		from baseline to t = 6 weeks	No