Trial Outcomes & Findings for 3-month Study of MSDC-0160 Effects on Brain Glucose Utilization, Cognition & Safety in Subjects With Alzheimer's Disease (NCT NCT01374438)

Last Updated: 2014-11-18

Results Overview

Investigate the effect of 150 mg daily MSDC-0160 vs placebo on 3-month change in brain glucose utilization using FDG-PET pre-specified regions of interest analysis referenced to cerebellum, including five bilateral regions: posterior cingulate, parietal cortex (angular gyrus), lateral temporal cortex, medial temporal cortex, and anterior cingulate-medial frontal cortex. Results are reported as Standardized Uptake Value Ratios. A change from baseline in the metabolic rate of glucose that is ≥0 indicates maintenance of brain glucose utilization, whereas values \<0 indicate a decline in brain glucose utilization.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

29 participants

Primary outcome timeframe

Days 1(baseline) and 91

Results posted on

2014-11-18

Participant Flow

Participant milestones

Participant milestones
Measure	MSDC-0160 Capsules MSDC tablets contained in #00 capsules MSDC-0160: MSDC-0160 150 mg capsules given once daily for 90 days	Placebo Capsules Placebo tablets contained in #00 capsules Placebo: Placebo capsules given once daily for 90 days
Overall Study STARTED	16	13
Overall Study COMPLETED	16	13
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

3-month Study of MSDC-0160 Effects on Brain Glucose Utilization, Cognition & Safety in Subjects With Alzheimer's Disease

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	MSDC-0160 Capsules n=16 Participants MSDC tablets contained in #00 capsules MSDC-0160: MSDC-0160 150 mg capsules given once daily for 90 days	Placebo Capsules n=13 Participants Placebo tablets contained in #00 capsules Placebo: Placebo capsules given once daily for 90 days	Total n=29 Participants Total of all reporting groups
Age, Continuous	72.3 years STANDARD_DEVIATION 8.8 • n=5 Participants	71.0 years STANDARD_DEVIATION 8.0 • n=7 Participants	71.7 years STANDARD_DEVIATION 8.3 • n=5 Participants
Sex: Female, Male Female	8 Participants n=5 Participants	8 Participants n=7 Participants	16 Participants n=5 Participants
Sex: Female, Male Male	8 Participants n=5 Participants	5 Participants n=7 Participants	13 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	2 Participants n=5 Participants	2 Participants n=7 Participants	4 Participants n=5 Participants
Race (NIH/OMB) White	14 Participants n=5 Participants	11 Participants n=7 Participants	25 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Presence of an Apolipoprotein E e4 allele Apo E e4 allele present	10 participants n=5 Participants	9 participants n=7 Participants	19 participants n=5 Participants
Presence of an Apolipoprotein E e4 allele Apo E e4 allelle absent	6 participants n=5 Participants	4 participants n=7 Participants	10 participants n=5 Participants
Mini-Mental State Examination Score	22.8 units on a scale STANDARD_DEVIATION 2.4 • n=5 Participants	25.2 units on a scale STANDARD_DEVIATION 2.1 • n=7 Participants	23.9 units on a scale STANDARD_DEVIATION 2.6 • n=5 Participants

PRIMARY outcome

Timeframe: Days 1(baseline) and 91

Population: Intent-to-treat

Outcome measures

Outcome measures
Measure	MSDC-0160 Capsules n=16 Participants MSDC tablets contained in #00 capsules MSDC-0160: MSDC-0160 150 mg capsules given once daily for 90 days	Placebo Capsules n=13 Participants Placebo tablets contained in #00 capsules Placebo: Placebo capsules given once daily for 90 days
Effects of MSDC-0160 on Cerebral Metabolic Glucose Rate or Placebo Over 12 Weeks in Pre-specified Regions of Interest Analysis Referenced to Cerebellum Ant. cing.-frontal cortex	0.00 Ratio Standard Deviation 0.02	-0.03 Ratio Standard Deviation 0.03
Effects of MSDC-0160 on Cerebral Metabolic Glucose Rate or Placebo Over 12 Weeks in Pre-specified Regions of Interest Analysis Referenced to Cerebellum Posterior cingulate	0.01 Ratio Standard Deviation 0.03	-0.02 Ratio Standard Deviation 0.03
Effects of MSDC-0160 on Cerebral Metabolic Glucose Rate or Placebo Over 12 Weeks in Pre-specified Regions of Interest Analysis Referenced to Cerebellum Parietal cingulate	0.01 Ratio Standard Deviation 0.02	-0.03 Ratio Standard Deviation 0.03
Effects of MSDC-0160 on Cerebral Metabolic Glucose Rate or Placebo Over 12 Weeks in Pre-specified Regions of Interest Analysis Referenced to Cerebellum Lateral temporal cortex	0.00 Ratio Standard Deviation 0.02	-0.02 Ratio Standard Deviation 0.03
Effects of MSDC-0160 on Cerebral Metabolic Glucose Rate or Placebo Over 12 Weeks in Pre-specified Regions of Interest Analysis Referenced to Cerebellum Medial temporal cortex	0.01 Ratio Standard Deviation 0.02	-0.01 Ratio Standard Deviation 0.02

SECONDARY outcome

Timeframe: Days 1 (baseline) and 91

Change from baseline in cognitive function, as determined by global cognitive function on a neuropsychological battery of 19 tests, following 3 months treatment with MSDC-0160 versus placebo. A summary measure of global cognitive function was constructed by converting raw scores from 19 individual tests into z-scores as described by Bennett DA, et al., The Rush Memory and Aging Project: study design and baseline characteristics of the study cohort, Neuroepidemiology. 2005;25(4):163-175.

Outcome measures

Outcome measures
Measure	MSDC-0160 Capsules n=16 Participants MSDC tablets contained in #00 capsules MSDC-0160: MSDC-0160 150 mg capsules given once daily for 90 days	Placebo Capsules n=13 Participants Placebo tablets contained in #00 capsules Placebo: Placebo capsules given once daily for 90 days
Change From Baseline in Global Cognitive Function Tests	-0.06 z-scores Standard Deviation 0.11	0.03 z-scores Standard Deviation 0.59

SECONDARY outcome

Timeframe: Days 1 (baseline) and 91

Population: One subject in the MSDC-0160 group and 2 subjects in the placebo group were not able to complete the ADAS-Cog tests at both study time points.

Alzheimer's Disease Assessment Scale - Cognitive Subscale, an assessment of cognitive ability. Scores on 11 individual tasks were summed to produce the reported total score, with a possible range of 0 (no impairment) to 70 (severe impairment).

Outcome measures

Outcome measures
Measure	MSDC-0160 Capsules n=15 Participants MSDC tablets contained in #00 capsules MSDC-0160: MSDC-0160 150 mg capsules given once daily for 90 days	Placebo Capsules n=11 Participants Placebo tablets contained in #00 capsules Placebo: Placebo capsules given once daily for 90 days
Change From Baseline in Cognitive Function as Determined by the ADAS-Cog Subscale	0.69 Scores on a scale Standard Deviation 3.62	2.21 Scores on a scale Standard Deviation 2.87

SECONDARY outcome

Timeframe: Days 1 (baseline) and 91

Population: One subject in the MSDC-0160 group and 2 subjects in the placebo group were not able to complete the executive function tests at both study time points.

Estimate of the effect of 3-months of MSDC-0160 treatment versus placebo on a 9-item executive function scale. A summary measure of executive function was constructed by converting raw scores from 9 individual tests into z-scores as described by Bennett DA, et al., The Rush Memory and Aging Project: study design and baseline characteristics of the study cohort, Neuroepidemiology. 2005;25(4):163-175.

Outcome measures

Outcome measures
Measure	MSDC-0160 Capsules n=15 Participants MSDC tablets contained in #00 capsules MSDC-0160: MSDC-0160 150 mg capsules given once daily for 90 days	Placebo Capsules n=11 Participants Placebo tablets contained in #00 capsules Placebo: Placebo capsules given once daily for 90 days
Change From Baseline in Cognitive Function as Estimate With the Executive Function Scale	-0.04 z-score Standard Deviation 0.25	0.00 z-score Standard Deviation 0.45

SECONDARY outcome

Timeframe: Days 1(baseline) and 91

Estimate the effect of 150 mg daily MSDC-0160 versus placebo on levels of high molecular weight adiponectin. Increases in HMW adiponectin suggest improved insulin sensitivity.

Outcome measures

Outcome measures
Measure	MSDC-0160 Capsules n=16 Participants MSDC tablets contained in #00 capsules MSDC-0160: MSDC-0160 150 mg capsules given once daily for 90 days	Placebo Capsules n=13 Participants Placebo tablets contained in #00 capsules Placebo: Placebo capsules given once daily for 90 days
Change From Baseline in HMW Adiponectin of MSDC-0160 or Placebo Over 12 Weeks	17822 micromol/L Standard Deviation 10940	795 micromol/L Standard Deviation 4477

Adverse Events

MSDC-0160 Capsules

Serious events: 1 serious events

Other events: 7 other events

Deaths: 0 deaths

Placebo Capsules

Serious events: 0 serious events

Other events: 5 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	MSDC-0160 Capsules n=16 participants at risk MSDC tablets contained in #00 capsules MSDC-0160: MSDC-0160 150 mg capsules given once daily for 90 days	Placebo Capsules n=13 participants at risk Placebo tablets contained in #00 capsules Placebo: Placebo capsules given once daily for 90 days
Respiratory, thoracic and mediastinal disorders Pneumonia	6.2% 1/16 • Number of events 1 • Collection of safety data began in August 2011, when the first subject was randomized, and continued until March 19, 2013, when all 29 subjects had completed all study activities. Subjects were asked to report any adverse events during each study visit.	0.00% 0/13 • Collection of safety data began in August 2011, when the first subject was randomized, and continued until March 19, 2013, when all 29 subjects had completed all study activities. Subjects were asked to report any adverse events during each study visit.
Infections and infestations Urinary tract infection	6.2% 1/16 • Number of events 1 • Collection of safety data began in August 2011, when the first subject was randomized, and continued until March 19, 2013, when all 29 subjects had completed all study activities. Subjects were asked to report any adverse events during each study visit.	0.00% 0/13 • Collection of safety data began in August 2011, when the first subject was randomized, and continued until March 19, 2013, when all 29 subjects had completed all study activities. Subjects were asked to report any adverse events during each study visit.

Other adverse events

Other adverse events
Measure	MSDC-0160 Capsules n=16 participants at risk MSDC tablets contained in #00 capsules MSDC-0160: MSDC-0160 150 mg capsules given once daily for 90 days	Placebo Capsules n=13 participants at risk Placebo tablets contained in #00 capsules Placebo: Placebo capsules given once daily for 90 days
Infections and infestations Urinary tract infection	6.2% 1/16 • Number of events 2 • Collection of safety data began in August 2011, when the first subject was randomized, and continued until March 19, 2013, when all 29 subjects had completed all study activities. Subjects were asked to report any adverse events during each study visit.	0.00% 0/13 • Collection of safety data began in August 2011, when the first subject was randomized, and continued until March 19, 2013, when all 29 subjects had completed all study activities. Subjects were asked to report any adverse events during each study visit.
Infections and infestations Nasopharyngitis	0.00% 0/16 • Collection of safety data began in August 2011, when the first subject was randomized, and continued until March 19, 2013, when all 29 subjects had completed all study activities. Subjects were asked to report any adverse events during each study visit.	7.7% 1/13 • Number of events 1 • Collection of safety data began in August 2011, when the first subject was randomized, and continued until March 19, 2013, when all 29 subjects had completed all study activities. Subjects were asked to report any adverse events during each study visit.
Gastrointestinal disorders Diarrhea	18.8% 3/16 • Number of events 3 • Collection of safety data began in August 2011, when the first subject was randomized, and continued until March 19, 2013, when all 29 subjects had completed all study activities. Subjects were asked to report any adverse events during each study visit.	7.7% 1/13 • Number of events 1 • Collection of safety data began in August 2011, when the first subject was randomized, and continued until March 19, 2013, when all 29 subjects had completed all study activities. Subjects were asked to report any adverse events during each study visit.
General disorders Peripheral Edema	6.2% 1/16 • Number of events 1 • Collection of safety data began in August 2011, when the first subject was randomized, and continued until March 19, 2013, when all 29 subjects had completed all study activities. Subjects were asked to report any adverse events during each study visit.	0.00% 0/13 • Collection of safety data began in August 2011, when the first subject was randomized, and continued until March 19, 2013, when all 29 subjects had completed all study activities. Subjects were asked to report any adverse events during each study visit.
Injury, poisoning and procedural complications Skin Laceration	6.2% 1/16 • Number of events 1 • Collection of safety data began in August 2011, when the first subject was randomized, and continued until March 19, 2013, when all 29 subjects had completed all study activities. Subjects were asked to report any adverse events during each study visit.	0.00% 0/13 • Collection of safety data began in August 2011, when the first subject was randomized, and continued until March 19, 2013, when all 29 subjects had completed all study activities. Subjects were asked to report any adverse events during each study visit.
Metabolism and nutrition disorders Hypoechoic nodule	0.00% 0/16 • Collection of safety data began in August 2011, when the first subject was randomized, and continued until March 19, 2013, when all 29 subjects had completed all study activities. Subjects were asked to report any adverse events during each study visit.	7.7% 1/13 • Number of events 1 • Collection of safety data began in August 2011, when the first subject was randomized, and continued until March 19, 2013, when all 29 subjects had completed all study activities. Subjects were asked to report any adverse events during each study visit.
Musculoskeletal and connective tissue disorders Pain in hip	6.2% 1/16 • Number of events 1 • Collection of safety data began in August 2011, when the first subject was randomized, and continued until March 19, 2013, when all 29 subjects had completed all study activities. Subjects were asked to report any adverse events during each study visit.	0.00% 0/13 • Collection of safety data began in August 2011, when the first subject was randomized, and continued until March 19, 2013, when all 29 subjects had completed all study activities. Subjects were asked to report any adverse events during each study visit.
Nervous system disorders Depression	6.2% 1/16 • Number of events 1 • Collection of safety data began in August 2011, when the first subject was randomized, and continued until March 19, 2013, when all 29 subjects had completed all study activities. Subjects were asked to report any adverse events during each study visit.	0.00% 0/13 • Collection of safety data began in August 2011, when the first subject was randomized, and continued until March 19, 2013, when all 29 subjects had completed all study activities. Subjects were asked to report any adverse events during each study visit.
Reproductive system and breast disorders Scrotal varicose vein rupture	6.2% 1/16 • Number of events 1 • Collection of safety data began in August 2011, when the first subject was randomized, and continued until March 19, 2013, when all 29 subjects had completed all study activities. Subjects were asked to report any adverse events during each study visit.	0.00% 0/13 • Collection of safety data began in August 2011, when the first subject was randomized, and continued until March 19, 2013, when all 29 subjects had completed all study activities. Subjects were asked to report any adverse events during each study visit.
Respiratory, thoracic and mediastinal disorders Nose bleed	0.00% 0/16 • Collection of safety data began in August 2011, when the first subject was randomized, and continued until March 19, 2013, when all 29 subjects had completed all study activities. Subjects were asked to report any adverse events during each study visit.	7.7% 1/13 • Number of events 1 • Collection of safety data began in August 2011, when the first subject was randomized, and continued until March 19, 2013, when all 29 subjects had completed all study activities. Subjects were asked to report any adverse events during each study visit.
Cardiac disorders Patent foramen ovale	0.00% 0/16 • Collection of safety data began in August 2011, when the first subject was randomized, and continued until March 19, 2013, when all 29 subjects had completed all study activities. Subjects were asked to report any adverse events during each study visit.	7.7% 1/13 • Number of events 1 • Collection of safety data began in August 2011, when the first subject was randomized, and continued until March 19, 2013, when all 29 subjects had completed all study activities. Subjects were asked to report any adverse events during each study visit.
Cardiac disorders QTcB elevation	0.00% 0/16 • Collection of safety data began in August 2011, when the first subject was randomized, and continued until March 19, 2013, when all 29 subjects had completed all study activities. Subjects were asked to report any adverse events during each study visit.	7.7% 1/13 • Number of events 1 • Collection of safety data began in August 2011, when the first subject was randomized, and continued until March 19, 2013, when all 29 subjects had completed all study activities. Subjects were asked to report any adverse events during each study visit.
Nervous system disorders Cognitive decline, subjective	0.00% 0/16 • Collection of safety data began in August 2011, when the first subject was randomized, and continued until March 19, 2013, when all 29 subjects had completed all study activities. Subjects were asked to report any adverse events during each study visit.	7.7% 1/13 • Number of events 1 • Collection of safety data began in August 2011, when the first subject was randomized, and continued until March 19, 2013, when all 29 subjects had completed all study activities. Subjects were asked to report any adverse events during each study visit.
Nervous system disorders Syncope, vasovagal	0.00% 0/16 • Collection of safety data began in August 2011, when the first subject was randomized, and continued until March 19, 2013, when all 29 subjects had completed all study activities. Subjects were asked to report any adverse events during each study visit.	7.7% 1/13 • Number of events 1 • Collection of safety data began in August 2011, when the first subject was randomized, and continued until March 19, 2013, when all 29 subjects had completed all study activities. Subjects were asked to report any adverse events during each study visit.

Additional Information

Dr. Jerry Colca

Metabolic Solutions Development Company

Phone: 269.343.8732

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: LTE60