Effects of ODM-109 on Respiratory Function in Patients With Amyotrophic Lateral Sclerosis

• Register: ClinicalTrials.gov
• Last refreshed on: 16 December 2017
• Main ID: NCT02487407
• Date of registration: 08/06/2015
• Prospective Registration: Yes
• Primary sponsor: Orion Corporation, Orion Pharma
• Public title: Effects of ODM-109 on Respiratory Function in Patients With Amyotrophic Lateral Sclerosis ALS
• Scientific title: Effects of ODM-109 on Respiratory Function in Patients With ALS. A Randomized, Double Blind, Placebo-controlled, Cross-over, 3-period, Multicenter Study With Open-label Follow-up Extension
• Date of first enrolment: July 2015
• Target sample size: 66
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT02487407
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Crossover Assignment. Primary purpose: Treatment. Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor).
• Phase: Phase 2

Countries of recruitment

Germany, Ireland, Netherlands, United Kingdom

Contacts

• Name: Merja Mäkitalo, CSD
• Affiliation: Finland

Key inclusion & exclusion criteria

Inclusion Criteria:

- Written informed consent (IC) for participation in the study will be obtained from the
subject (or from the subject's next of kin, caregiver, or other legally acceptable
representative in case the study subject him/herself cannot sign the IC due to severe
muscle weakness).

- Age of at least 18 years.

- Male or female subjects with diagnosis of laboratory supported probable, probable or
definite ALS according to El Escorial revised criteria (Brooks BR et al., 2000). Full
electromyogram (EMG) report available compatible with ALS according to an experienced
neurophysiologist.

- Ability to swallow the study treatment capsules.

- An upright (sitting position) SVC between 60-90% of the predicted value for age,
height and sex at screening visit.

- Normal oxygen saturation during daytime (measure of = 95% when steady state has been
reached with a reliable read) in sitting position measured by pulse oximetry.

- Disease duration from symptom onset (defined by first muscle weakness or dysarthria)
of 12-48 months.

- Using riluzole. The dose must have been stable for at least 4 weeks prior to screening
at a dose of 50 mg b.i.d.

Exclusion Criteria:

- Subject in whom other causes of neuromuscular weakness have not been excluded.

- Subject with a diagnosis of another neurodegenerative disease (e.g. Parkinson's or
Alzheimer's disease).

- Assisted ventilation or gastrostomy of any type during the preceding 3 months prior to
screening or predicted to be required within the randomised, double-blind cross-over
part of the study.

- Recorded diagnosis or evidence of major psychiatric diagnosis, significant cognitive
impairment or clinically evident dementia.

- Any major surgery within 1 month before the screening visit or patients who are
scheduled for any major surgery during the planned study period.

- Potassium < 3.7 mmol/l or > 5.5 mmol/l at screening.

- Creatinine > 170 µmol/l at screening or on dialysis.

- Blood haemoglobin < 10 g/dl at screening.

- Clinically significant hepatic impairment at the discretion of the investigator.

- Women of reproductive age without a negative pregnancy test and without a commitment
to using an acceptable method of barrier or hormonal contraception (e.g. condoms,
diaphragms, oral contraceptives and long acting progestin agents), if sexually active
during the study, and for 1 month after the last dose of the study treatment. Women
who are postmenopausal (1 year since last menstrual cycle), surgically sterilised or
who have undergone a hysterectomy are considered not to be reproductive and can be
included.

- Known hypersensitivity to levosimendan.

- Administration of levosimendan within 30 days prior to screening visit.

- Patients with history of botulinum toxin treatment for any reason.

- Patients with known history of human immunodeficiency virus infection.

- History of significant arrhythmias or other cardiac events

- Any other clinically significant cardiovascular, pulmonary, gastrointestinal, hepatic,
renal, neurological or psychiatric disorder or any other major concurrent illness that
in the opinion of the investigator could interfere with the interpretation of the
study results or constitute a health risk for the subject if he/she took part in the
study.

- Blood donation or loss of significant amount of blood within 60 days prior to
screening.

- Participation in a clinical trial with any experimental treatment within 30 days prior
to the screening visit or previous participation in the present study.

- Any other condition that in the opinion of the investigator could interfere with the
interpretation of the study results or constitute a health risk for the subject if
he/she took part in the study.



Age minimum: 18 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Amyotrophic Lateral Sclerosis

Intervention(s)

Drug: ODM-109

Drug: Placebo for ODM-109

Primary Outcome(s)

Slow vital capacity SVC [Time Frame: 9 months]

Secondary Outcome(s)

Revised ALS Functional Rating Scale ALSFRS-R [Time Frame: 9 months]

Hand grip strength and submaximal hand grip strength endurance [Time Frame: 3 months]

Fatigue assessment [Time Frame: 3 months]

Changes in subject's clinical condition (relative to the baseline/day 1 of the given treatment period) will be assessed using the Clinical Global Impression of Change (CGI-C) [Time Frame: 3 months]

Oxygen saturation [Time Frame: 9 months]

Sniff nasal pressure SNP [Time Frame: 9 months]

Determination of subject's acetylation status [Time Frame: 1 day (once at baseline)]

Quality of life [Time Frame: 9 months]

The concentrations of ODM-109, OR-1855 and OR-1896 [Time Frame: 3 months]

Secondary ID(s)

3119001

Source(s) of Monetary Support

Please refer to primary and secondary sponsors