Trial Outcomes & Findings for Safety and Efficacy of ORM-12741 in Patients With Alzheimer's Disease (NCT NCT01324518)

NCT ID: NCT01324518

Last Updated: 2021-04-28

Results Overview

Adverse events from start of ORM-12741 treatment until end of study visit.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 100 participants
• Primary outcome timeframe: 3 months
• Results posted on: 2021-04-28

Participant Flow

This study was conducted in 4 countries (18 centres): Finland, Poland, Romania and Spain. Of these, 1 centre screened but did not randomise any subjects. Study period was 27 Apr 2011-21 Sep 2012 (first subject first visit to last subject last visit).

A total of 132 subjects were screened and 100 were randomized to 3 treatment groups. 30 patients were excluded prior randomization due to inclusion/exclusion criteria, 2 due to personal reasons.

Participant milestones

Measure	Low Dose of ORM-12741 ORM-12741: 60mg twice a day	High Dose of ORM-12741 ORM-12741: 200mg twice a day	Placebo Placebo for ORM-12741: Placebo twice a day
Overall Study STARTED	33	33	34
Overall Study COMPLETED	28	30	33
Overall Study NOT COMPLETED	5	3	1

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Safety and Efficacy of ORM-12741 in Patients With Alzheimer's Disease

Baseline characteristics by cohort

Measure	Low Dose of ORM-12741 n=33 Participants ORM-12741: 60mg twice a day	High Dose of ORM-12741 n=33 Participants ORM-12741: 200mg twice a day	Placebo n=34 Participants Placebo for ORM-12741: Placebo twice a day	Total n=100 Participants Total of all reporting groups
Age, Continuous	71.8 years STANDARD_DEVIATION 8.2 • n=5 Participants	71.8 years STANDARD_DEVIATION 6.8 • n=7 Participants	72.3 years STANDARD_DEVIATION 8.5 • n=5 Participants	72.0 years STANDARD_DEVIATION 7.8 • n=4 Participants
Sex: Female, Male Female	19 Participants n=5 Participants	23 Participants n=7 Participants	17 Participants n=5 Participants	59 Participants n=4 Participants
Sex: Female, Male Male	14 Participants n=5 Participants	10 Participants n=7 Participants	17 Participants n=5 Participants	41 Participants n=4 Participants

PRIMARY outcome

Timeframe: 3 months

Adverse events from start of ORM-12741 treatment until end of study visit.

Outcome measures

Measure	Low Dose of ORM-12741 n=33 Participants ORM-12741: 60mg twice a day	High Dose of ORM-12741 n=33 Participants ORM-12741: 200mg twice a day	Placebo n=34 Participants Placebo for ORM-12741: Placebo twice a day
Number of Participants With Adverse Events	18 Participants	21 Participants	21 Participants

PRIMARY outcome

Timeframe: 3 months

Population: per protocol population

The Cognitive Drug Research (CDR) computerised battery tests is designed to evaluate the effects of novel compounds on the quality of cognitive functioning. Quality of Episodic Memory measures the capability of maintaining information in episodic memory and is assessed as the sum of sensitivity indices from 4 memory tasks on the CDR computerised battery tests. Values are calculated by a computer and higher scores mean better outcome.

Outcome measures

Measure	Low Dose of ORM-12741 n=24 Participants ORM-12741: 60mg twice a day	High Dose of ORM-12741 n=26 Participants ORM-12741: 200mg twice a day	Placebo n=28 Participants Placebo for ORM-12741: Placebo twice a day
Quality of Episodic Memory	100.7 Index score Standard Deviation 92.2	85.0 Index score Standard Deviation 59.6	46.3 Index score Standard Deviation 62.4

PRIMARY outcome

Timeframe: 3 months

Population: per protocol population

The Cognitive Drug Research (CDR) computerised battery tests is designed to evaluate the effects of novel compounds on the quality of cognitive functioning. Quality of Working Memory measures the capability of maintaining information in working memory and is assessed as the sum of sensitivity indices from 2 memory tasks on the CDR computerised battery tests. Values are calculated by a computer and higher scores mean better outcome.

Outcome measures

Measure	Low Dose of ORM-12741 n=24 Participants ORM-12741: 60mg twice a day	High Dose of ORM-12741 n=26 Participants ORM-12741: 200mg twice a day	Placebo n=28 Participants Placebo for ORM-12741: Placebo twice a day
Quality of Working Memory	1.20 Index score Standard Deviation 0.53	1.18 Index score Standard Deviation 0.47	0.82 Index score Standard Deviation 0.59

PRIMARY outcome

Timeframe: 3 months

Population: per protocol population

The Cognitive Drug Research (CDR) computerised battery tests is designed to evaluate the effects of novel compounds on the quality of cognitive functioning. Quality of Memory is a combination of outcome measures Quality of Working Memory & Quality of Episodic Memory. Values are calculated by a computer and higher scores mean better outcome.

Outcome measures

Measure	Low Dose of ORM-12741 n=24 Participants ORM-12741: 60mg twice a day	High Dose of ORM-12741 n=26 Participants ORM-12741: 200mg twice a day	Placebo n=28 Participants Placebo for ORM-12741: Placebo twice a day
Quality of Memory	216.53 Index score Standard Deviation 133.15	196.37 Index score Standard Deviation 93.72	117.15 Index score Standard Deviation 104.30

PRIMARY outcome

Timeframe: 3 months

Population: per protocol population

The Cognitive Drug Research (CDR) computerised battery tests is designed to evaluate the effects of novel compounds on the quality of cognitive functioning. Speed of Memory is assessed as the sum of speed measures from 2 memory tasks and 2 recognition tasks on the CDR computerised battery tests. Values are calculated by a computer and higher scores mean better outcome.

Outcome measures

Measure	Low Dose of ORM-12741 n=24 Participants ORM-12741: 60mg twice a day	High Dose of ORM-12741 n=26 Participants ORM-12741: 200mg twice a day	Placebo n=28 Participants Placebo for ORM-12741: Placebo twice a day
Speed of Memory	8287.8 msec Standard Deviation 3898.2	8930.30 msec Standard Deviation 5379.5	8082.2 msec Standard Deviation 4064.1

PRIMARY outcome

Timeframe: 3 months

Population: per protocol population

The Cognitive Drug Research (CDR) computerised battery tests is designed to evaluate the effects of novel compounds on the quality of cognitive functioning. Power of attention measures speed and attention and is assessed from 3 attentional tasks on the CDR computerised battery tests. Values are calculated by a computer and higher scores mean better outcome.

Outcome measures

Measure	Low Dose of ORM-12741 n=25 Participants ORM-12741: 60mg twice a day	High Dose of ORM-12741 n=26 Participants ORM-12741: 200mg twice a day	Placebo n=28 Participants Placebo for ORM-12741: Placebo twice a day
Power of Attention	1940.3 msec Standard Deviation 533.3	1978.0 msec Standard Deviation 1040.4	2077.9 msec Standard Deviation 995.8

PRIMARY outcome

Timeframe: 3 months

Population: per protocol population

The Cognitive Drug Research (CDR) computerised battery tests is designed to evaluate the effects of novel compounds on the quality of cognitive functioning. Continuity of attention measures speed and accuracy and is calculated from 3 attentional tasks on the CDR computerised battery tests. Values are calculated by a computer and higher scores mean better outcome.

Outcome measures

Measure	Low Dose of ORM-12741 n=25 Participants ORM-12741: 60mg twice a day	High Dose of ORM-12741 n=26 Participants ORM-12741: 200mg twice a day	Placebo n=28 Participants Placebo for ORM-12741: Placebo twice a day
Continuity of Attention	85.7 Index score Standard Deviation 11.0	84.8 Index score Standard Deviation 15.3	79.7 Index score Standard Deviation 21.2

SECONDARY outcome

Timeframe: 3 months

Population: per protocol population

The total score of Neuropsychiatric Inventory (NPI) was assessed by a caregiver interview. 10 behavioral areas were included: Delusions, Hallucinations, Agitation/Aggression, Depression/Dysphoria, Anxiety, Elation/Euphoria, Apathy/Indifference, Disinhibition, Irritability/Lability, and Aberrant Motor Behaviour. Higher scores mean worse outcome. Minimum value 0, maximum value 120.

Outcome measures

Measure	Low Dose of ORM-12741 n=25 Participants ORM-12741: 60mg twice a day	High Dose of ORM-12741 n=26 Participants ORM-12741: 200mg twice a day	Placebo n=28 Participants Placebo for ORM-12741: Placebo twice a day
NPI Total Score	14.7 score on a scale Standard Deviation 9.1	13.7 score on a scale Standard Deviation 8.9	20.2 score on a scale Standard Deviation 19.0

SECONDARY outcome

Timeframe: 3 months

Population: per protocol population

Caregiver distress score generated by adding together the scores of individual NPI distress questions of Neuropsychiatric Inventory NPI. Higher scores mean worse outcome. Minimum value 0, maximum value 120.

Outcome measures

Measure	Low Dose of ORM-12741 n=25 Participants ORM-12741: 60mg twice a day	High Dose of ORM-12741 n=26 Participants ORM-12741: 200mg twice a day	Placebo n=28 Participants Placebo for ORM-12741: Placebo twice a day
Caregiver Distress Score	9.2 score on a scale Standard Deviation 6.0	8.0 score on a scale Standard Deviation 4.3	11.0 score on a scale Standard Deviation 10.4

SECONDARY outcome

Timeframe: 3 months

Population: M-ITT population

ORM-12741 plasma trough concentrations at week 12.

Outcome measures

Measure	Low Dose of ORM-12741 n=29 Participants ORM-12741: 60mg twice a day	High Dose of ORM-12741 n=31 Participants ORM-12741: 200mg twice a day	Placebo n=32 Participants Placebo for ORM-12741: Placebo twice a day
Pharmacokinetics of ORM-12741	18.4 ng/ml Standard Deviation 13.9	61.0 ng/ml Standard Deviation 45.9	0 ng/ml Standard Deviation 0

Adverse Events

Low Dose of ORM-12741

Serious events: 0 serious events

Other events: 8 other events

Deaths: 0 deaths

High Dose of ORM-12741

Serious events: 1 serious events

Other events: 14 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 16 other events

Deaths: 0 deaths

Serious adverse events

Measure	Low Dose of ORM-12741 n=33 participants at risk ORM-12741: 60mg twice a day	High Dose of ORM-12741 n=33 participants at risk ORM-12741: 200mg twice a day	Placebo n=34 participants at risk Placebo for ORM-12741: Placebo twice a day
Hepatobiliary disorders Cholestasis	0.00% 0/33 • 3 months	3.0% 1/33 • Number of events 1 • 3 months	0.00% 0/34 • 3 months

Other adverse events

Measure	Low Dose of ORM-12741 n=33 participants at risk ORM-12741: 60mg twice a day	High Dose of ORM-12741 n=33 participants at risk ORM-12741: 200mg twice a day	Placebo n=34 participants at risk Placebo for ORM-12741: Placebo twice a day
Gastrointestinal disorders Diarrhoea	6.1% 2/33 • Number of events 3 • 3 months	3.0% 1/33 • Number of events 1 • 3 months	5.9% 2/34 • Number of events 3 • 3 months
Gastrointestinal disorders Nausea	6.1% 2/33 • Number of events 2 • 3 months	3.0% 1/33 • Number of events 1 • 3 months	8.8% 3/34 • Number of events 5 • 3 months
Gastrointestinal disorders Vomiting	3.0% 1/33 • Number of events 1 • 3 months	12.1% 4/33 • Number of events 6 • 3 months	2.9% 1/34 • Number of events 1 • 3 months
General disorders Irritability	0.00% 0/33 • 3 months	6.1% 2/33 • Number of events 2 • 3 months	8.8% 3/34 • Number of events 3 • 3 months
Infections and infestations Urinary tract infection	3.0% 1/33 • Number of events 2 • 3 months	15.2% 5/33 • Number of events 5 • 3 months	8.8% 3/34 • Number of events 3 • 3 months
Nervous system disorders Headache	6.1% 2/33 • Number of events 4 • 3 months	3.0% 1/33 • Number of events 1 • 3 months	11.8% 4/34 • Number of events 8 • 3 months

Additional Information

Clinical Study Director

Orion Global Clinical Operations

Email: jutta.hanninen@orionpharma.com

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place