Opioid Induced Gait Variability

The study is designed as an experimental single center, double-blind treatment, cross-over study with inert placebo, Tapentadol (Palexia Depot), and Tramadolhydrochlorid (Mandolgin Retard), with a minimum of 7days wash-out periods.

At day 1 (Visit 1), baseline measurements are carried out before tablet administration. Immediately after baseline measurements one tablet is administered, and hourly measurements are performed for 6 hours. Subsequently all participants enter a minimum 7 day washout period, after which they return to the facility to repeat the procedures at Visit 2 (day 8+) and Visit 3 (day 15+). The order of treatments will be randomized (1:1:1).

Inclusion criteria

Healthy subjects:

• In general good health, in the opinion of the Investigator, based on medical history and physical examination.
• Ability to comprehend and a willingness to provide written informed consent
• Age between 50 and 75 years
• No opioid usage 3 months prior to the study
• No musculoskeletal pain requiring medical attention during the previous 3 months
• Willing and able to complete study visits and procedures
• Willing to hold activity, exercise level, and concurrent treatments/therapies generally consistent during the study
• A body mass index (BMI) of ≤30

Patients with knee osteoarthritis (OA)

• Diagnosis of knee OA
• Ability to comprehend and a willingness to provide written informed consent
• Age between 50 and 75 years
• No opioid usage 3 months prior to the study
• Knee pain of at least 40 mm on a 0-100 mm visual analog scale (without analgesics) representing the average pain intensity during the previous week
• Willing to discontinue all pain medications 24 hours before and during examination visits
• Willing and able to complete study visits and procedures
• Willing to hold activity, exercise level, and concurrent treatments/therapies generally consistent during the study
• In general good health, in the opinion of the Investigator, based on medical history and physical examination.
• A body mass index (BMI) of ≤30

Exclusion criteria

The same exclusion criteria apply for both healthy subjects and patients with knee osteoarthritis:

• Clinical signs of gait ataxia assessed by clinical neurological examination
• Independent or unsteady walking (i.e. dependence on walking device or stumbling gait)
• Counter indications to either of the investigational products, including but not restricted to:

• Allergy towards one or more of the investigational products or their excipient(s).
• Significant respiratory depression
• Current or serious asthma
• Hypercapnia
• Suspected or diagnosed paralytic ileus
• Acute intoxication by alcohol, hypnotica, centrally acting analgesics, psychopharmaca or other pharmaceuticals.
• Renal dysfunction
• Hepatic dysfunction
• Diseases of the biliary tract
• Acute pancreatitis
• Usage of monoamine oxidase inhibitors within the last 14 days
• Galactose intolerance
• Lactase deficiency
• Glucose/galactose malabsorption
• Epilepsy
• Previous usage of opioids without pain reliving effect.
• Patients who have a documented history of an allergic reaction or a clinically significant intolerance to opioids
• Malignant pain
• Excessive joint laxity in the lower extremities indicative of functional ligamentous deficiency.
• Dependency of walking aid (stick, cane, roller etc.).
• Positive Clock Drawing Test
• Abuse of alcohol, medicine and narcotics within past 5 years.
• History of symptoms of autoimmune disorders
• Diabetes
• Pregnancy or breast feeding
• History, diagnosis, or signs and symptoms of clinically significant neurological disease
• History, diagnosis, signs or symptoms of any clinically significant psychiatric disorder