NCT02139098.

Trial name or title	Phase III Study on Alternative Dosing Regimens in the Pharmacotherapy of Mild to Moderate Insomnia
Methods	Randomised, double‐blind, controlled trial
Participants	Aged: 18‐69 years Gender: men and women Accepts healthy volunteers: no Inclusion criteria: aged 18‐69 years; fluent in German language; provide written informed consent; ability to understand the explanations and instructions given by the study physician and the investigator Exclusion criteria: sleep disorders caused by medical factors (e.g. sleep apnoea, restless legs syndrome, narcolepsy, substance‐induced insomnia); contraindications to study medication intake according to the information sheet for health professionals (Summary of medicinal Product Characteristics, Fachinformation in Germany) assessed by physical examination (including ECG) and medical history; allergies to amitriptyline hydrochloride or any of its ingredients; allergies to zolpidem or any of its ingredients; acute intoxication with alcohol, analgesics, hypnotics or any other psychotropic drug; urinary retention; delirium; untreated closed‐angle glaucoma; prostatic hyperplasia; pyloric stenosis; paralytic ilius; suicidal thoughts; liver/kidney/pulmonary insufficiency; myasthenia gravis; hypokalaemia; bradycardia; coronary heart disease, cardiac arrhythmias, long QT syndrome or other clinically relevant cardiac disorders; increased risk of seizures/history of seizures; substance dependence syndrome/history of substance dependence syndrome; allergies to ingredients of placebo or novel‐tasting drink; currently pregnant (verified by urine pregnancy test) or lactating; people scoring ≥ 12 on the Epworth Sleepiness Scale; people scoring < 8 or > 21 on the ISI; people with a mental disorder as verified by the SCID (major depression, psychosis, brain injury, substance abuse or dependency syndrome during the last 6 months before V1); nicotine consumption > 10 cigarettes/day; unwillingness to refrain from alcohol consumption throughout the study; concomitant medication interfering with study medication intake due to potential interactions (all psychotropic medication including analgesics and muscle relaxants, hypericum derivatives, antihypertensives, antiarrhythmic agents, antibiotics, cisapride, antimalaria drugs, diuretics, imidazole antifungals, cumarin derivatives, antihistamines, calcium channel blockers, medications that enlarge the QT interval or may lead to hypokalaemia); change in concomitant medication regimen during the last 2 weeks prior to visit 1 or after randomisation; intake of psychotropic medication during the last 3 months; participation in any other clinical trial 3 months prior to visit 1; women of childbearing age not using 2 highly effective contraceptive methods; employee of the sponsor or the principal investigator
Interventions	Intervention: amitriptyline flexible dosing 50 mg capsule before going to bed on 8 out of 17 nights/placebo Intervention: zolpidem flexible dosing 5 mg capsule before going to bed on 8 out of 17 nights/placebo Active comparator: amitriptyline fixed dosing 50 mg capsule before going to bed on 8 out of 17 nights Active comparator: zolpidem fixed dosing 5 mg capsule before going to bed on 8 out of 17 nights Active comparator: amitriptyline continuous dosing 50 mg capsule before going to bed on 13 out of 17 nights
Outcomes	Primary outcomes Objective total sleep time assessed by PSG (change from baseline to day 10 after first medication intake) Objective sleep onset latency assessed by PSG (change from baseline to day 10 after first medication intake) Self‐reported total sleep time assessed by sleep diary (change from baseline to day 10 after first medication intake) assessed by sleep diary Self‐reported sleep onset latency (change from baseline to day 10 after first medication intake) assessed by sleep diary Secondary outcomes Percentage of REM sleep assessed by PSG (change from baseline to day 10 after first medication intake) REM onset latency assessed by PSG (change from baseline to day 10 after first medication intake) Objective sleep efficiency assessed by actigraphy (change from baseline to day 17 after first medication intake) Objective total sleep time assessed by actigraphy (change from baseline to day 17 after first medication intake) Self‐reported total sleep time assessed by sleep diary (change from baseline to day 18 after first medication intake) Self‐reported sleep onset latency assessed by sleep diary (change from baseline to day 18 after first medication intake) Self‐reported sleep onset latency (evaluation) assessed by sleep diary (change from baseline to day 18 after first medication intake)
Starting date	May 2014
Contact information	Professor Winfried Rief; rief@staff.uni‐marburg.de
Notes	Estimate study completion date December 2017

DSM: Diagnostic and Statistical Manual of Mental Disorders; ECG: electrocardiogram; ISI: Insomnia Severity Index; PQSI: Pittsburgh Quality Sleep Index; PSG: polysomnography; REM: rapid eye movement; SCID: Structured Clinical Interview for Depression.