Tamoxifen in Duchenne muscular dystrophy

Recruitment & Eligibility

Status: Completed

Sex: Not specified

Target Recruitment: 18

Inclusion Criteria

Group A (ambulant patients)
- Documented diagnosis of DMD by mutation analysis in the dystrophin gene or by
substantially reduced levels of dystrophin protein (i.e. absent or <5% of
normal) on Western blot or immunostaining
- Stable treatment with glucocorticoids >6 months (no significant change in
dosage (>0.2mg/kg)) at screening; dosing adaptations according to weight change
are allowed
- Male gender
- 6.5 to 12 years of age at time of screening
- weight >20kg
- ambulant patients
- able to walk at least 350 meters in 6 minute walking distance test without
assistance at screening
- MFM D1 subdomain of the MFM scale >40% at screening
- Ability to provide informed consent and to comply with study requirements
- Patients harbouring a nonsense mutation treatable with the approved drug
ataluren should be under stable ataluren treatment for at least 3 months or in
case of non tolerance being off ataluren treatment for at least 3 months before
screening Group B (non-ambulant patients)
- Documented diagnosis of DMD by mutation analysis in the dystrophin gene or by
substantially reduced levels of dystrophin protein (i.e. absent or <5% of
normal) on Western blot or immunostaining
- not using glucocorticoids for >6 months
- Male gender
- non-ambulant patients (walking distance less than 10 meters)
- 10 to 16 years of age at time of screening
- Ability to provide informed consent and to comply with study
requirements7S8S9S
Open label Extension: Recent participation and completion of TAMDMD study

Exclusion Criteria

- Known individual hypersensitivity or allergy to tamoxifen or other
ingredients /excipients of IMP
- Female gender
- Use of tamoxifen or testosterone within the last 3 months
- Known or suspected malignancy
- Other chronic disease or clinically relevant limitation of renal, liver or
heart function (as judged by the Investigator)
- Known or suspected non-compliance
- Any injury which may impact functional testing, e.g. upper or lower limb
fracture
- Planned or expected spinal fusion surgery during the study period (as judged
by the Investigator; i.e. due to rapid progressing scoliosis), previous spinal
fusion surgery is allowed if it took place more than 6 month prior to screening.
- Inability to follow the procedures of the study, e.g. due to language
problems, psychological disorders of the participant/parents (as judged by the
investigator)
- Concomitant participation in any other interventional trial (and up to 3
months prior to screening)
- Use of CYP2D6 inhibitors or of CYP3A4 inducers (apart from
glucocorticoids), platelet aggregation inhibitors and coumarin-type
anti-coagulants
- Use of drugs metabolized by CYP2C9, such as phenprocoumon, phenytoin,
warfarin, celecobix, fluvastatin, ginko biloba, st. John's wort and
sulfamethoxazol.
- Galactosemia (lack of galactose-1-phosphat-uridylyltransferase or
UDP-galactose-4-epimerase or galactokinase; Fanconi-Bickel-syndrome);
congenital lack of lactase; glucose-galactose malabsorption.
- Presence of one or more of the following eye disorders: cataract,
retinopathia, optic neuropathy, alteration of the cornea.
Presence of one or more of the following laboratory abnormalities: anaemia,
thrombocytopenia, leukopenia, neutropenia or agranulocytosis.Group A:
- Glucocorticoid naïve patients
- Start of glucocorticoid treatment or change in dosage <6 month prior to
screening (dosing adaptations according to weight change are allowed)Group B:
- Glucocorticoid treated patients or patients that stopped steroid treatment <6
month prior to screening
- Participation in any other interventional trial