Trial Outcomes & Findings for Efficacy and Safety of MK-7622 as Adjunct Therapy in Participants With Alzheimer's Disease (MK-7622-012) (NCT NCT01852110)

Last Updated: 2018-09-18

Results Overview

Mean change from baseline at week 12 was assessed for ADAS-Cog11 score. ADAS-Cog11 measures cognition by assessing 11 metrics impaired in Alzheimer's Disease (AD): speech; speech comprehension; word finding; word recall; object/finger naming; orientation; obeying commands; ideational praxis; constructional praxis; word recognition; and remembering instruction. For each metric, scores range from 0 (no impairment) to (depending on the metric) either 5 (8 metrics), 8, 10, or 12 (1 metric each); higher scores indicate more severe impairment. Individual scores sum to a total ADAS-Cog11 score, ranging from 0-70. Higher total scores indicate greater cognitive impairment and AD severity. Further, increases in AD severity over time would be reflected by increases in ADAS-Cog11 score.

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

240 participants

Primary outcome timeframe

Baseline and week 12

Results posted on

2018-09-18

Participant Flow

Number of Participants Screened: 505 Number of Participants Randomized: 240

Stage 1 interim analysis met the prespecified futility threshold for the primary efficacy endpoint, satisfying the clinical criteria for early trial termination (futility). As a result, the trial was terminated at Stage 1; did not proceed to Stage 2. In stage 1: 1 randomized participant received no study medication (MK-7622 High Dose-45 mg arm).

Participant milestones

Participant milestones
Measure	MK-7622 High Dose - 45 mg (Stage 1) Single 45 mg MK-7622 capsule once daily, taken orally. Dose escalated as follows: 15 mg MK-7622 once daily for 1 week; 30 mg MK-7622 once daily for 1 week; and 45 mg MK-7622 once daily for the remainder of treatment.	Placebo (Stage 1) Matching placebo to MK-7622 capsule once daily, taken orally.
Overall Study STARTED	120	120
Overall Study Treated	119	120
Overall Study COMPLETED	70	74
Overall Study NOT COMPLETED	50	46

Reasons for withdrawal

Reasons for withdrawal
Measure	MK-7622 High Dose - 45 mg (Stage 1) Single 45 mg MK-7622 capsule once daily, taken orally. Dose escalated as follows: 15 mg MK-7622 once daily for 1 week; 30 mg MK-7622 once daily for 1 week; and 45 mg MK-7622 once daily for the remainder of treatment.	Placebo (Stage 1) Matching placebo to MK-7622 capsule once daily, taken orally.
Overall Study Adverse Event	12	5
Overall Study Lost to Follow-up	1	3
Overall Study Non-compliance with Study Drug	2	1
Overall Study Physician Decision	1	0
Overall Study Protocol Violation	0	1
Overall Study Study Terminated by Sponsor	30	32
Overall Study Withdrawal by Subject	4	4

Baseline Characteristics

Includes only randomized participants receiving ≥1 dose of study medication, having a baseline ADAS-Cog11 assessment.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	MK-7622 High Dose - 45 mg (Stage 1) n=119 Participants Single 45 mg MK-7622 capsule once daily, taken orally. Dose escalated as follows: 15 mg MK-7622 once daily for 1 week; 30 mg MK-7622 once daily for 1 week; and 45 mg MK-7622 once daily for the remainder of treatment.	Placebo (Stage 1) n=120 Participants Matching placebo to MK-7622 capsule once daily, taken orally.	Total n=239 Participants Total of all reporting groups
Age, Continuous	72.5 Years STANDARD_DEVIATION 7.1 • n=119 Participants	71.7 Years STANDARD_DEVIATION 8.3 • n=120 Participants	72.1 Years STANDARD_DEVIATION 7.7 • n=239 Participants
Sex: Female, Male Female	61 Participants n=119 Participants	68 Participants n=120 Participants	129 Participants n=239 Participants
Sex: Female, Male Male	58 Participants n=119 Participants	52 Participants n=120 Participants	110 Participants n=239 Participants
11-item Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog11) Score	21.8 Score on a Scale STANDARD_DEVIATION 7.05 • n=119 Participants • Includes only randomized participants receiving ≥1 dose of study medication, having a baseline ADAS-Cog11 assessment.	23.6 Score on a Scale STANDARD_DEVIATION 8.73 • n=120 Participants • Includes only randomized participants receiving ≥1 dose of study medication, having a baseline ADAS-Cog11 assessment.	22.7 Score on a Scale STANDARD_DEVIATION 7.95 • n=239 Participants • Includes only randomized participants receiving ≥1 dose of study medication, having a baseline ADAS-Cog11 assessment.
Alzheimer's Disease Cooperative Study-Activities of Daily Living (ADCS-ADL) Score	60.7 Score on a Scale STANDARD_DEVIATION 11.18 • n=119 Participants • Includes only randomized participants receiving ≥1 dose of study medication, having a baseline ADCS-ADL assessment.	59.4 Score on a Scale STANDARD_DEVIATION 11.89 • n=119 Participants • Includes only randomized participants receiving ≥1 dose of study medication, having a baseline ADCS-ADL assessment.	59.9 Score on a Scale STANDARD_DEVIATION 11.72 • n=238 Participants • Includes only randomized participants receiving ≥1 dose of study medication, having a baseline ADCS-ADL assessment.
Composite Cognition Score-3 Domain (CCS-3D)	-0.11 z-score STANDARD_DEVIATION 0.739 • n=108 Participants • Includes only randomized participants receiving ≥1 dose of study medication, having a baseline CCS-3D assessment.	0.02 z-score STANDARD_DEVIATION 0.816 • n=110 Participants • Includes only randomized participants receiving ≥1 dose of study medication, having a baseline CCS-3D assessment.	-0.039 z-score STANDARD_DEVIATION 0.776 • n=218 Participants • Includes only randomized participants receiving ≥1 dose of study medication, having a baseline CCS-3D assessment.

PRIMARY outcome

Timeframe: Baseline and week 12

Population: All randomized participants in Stage 1 receiving ≥1 dose of study medication, having either a baseline or 12-week ADAS-Cog11 assessment.

Outcome measures

Outcome measures
Measure	MK-7622 High Dose - 45 mg (Stage 1) n=119 Participants Single 45 mg MK-7622 capsule once daily, taken orally. Dose escalated as follows: 15 mg MK-7622 once daily for 1 week; 30 mg MK-7622 once daily for 1 week; and 45 mg MK-7622 once daily for the remainder of treatment.	Placebo (Stage 1) n=120 Participants Matching placebo to MK-7622 capsule once daily, taken orally.	Placebo (Stage 2) Matching placebo to MK-7622 capsule once daily, taken orally.	MK-7622 Mid Dose - 15 mg (Stage 2) Single 15 mg MK-7622 capsule once daily, taken orally.	MK-7622 High Dose - 45 mg (Stage 2) Single 45 mg MK-7622 capsule once daily, taken orally. Dose escalated as follows: 15 mg MK-7622 once daily for 1 week; 30 mg MK-7622 once daily for 1 week; and 45 mg MK-7622 once daily for the remainder of treatment.	Placebo (Stage 2) Matching placebo to MK-7622 capsule once daily, taken orally.
Change From Baseline in the 11-item Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog11) Score at Week 12 (Stage 1, MK-7622 45 mg Versus Placebo)	0.39 Score on a Scale Standard Error 0.440	0.21 Score on a Scale Standard Error 0.416	—	—	—	—

PRIMARY outcome

Timeframe: Baseline and week 12

Population: Per study protocol, the analysis population was to include only randomized participants in Stage 2 receiving ≥1 dose of placebo, MK-7622 - 15 mg, or MK-7622 - 45 mg, having either a baseline or 12-week ADAS-Cog11 assessment. Study terminated before Stage 2 enrollment; no data were collected for this outcome measure.

Outcome measures

Outcome data not reported

PRIMARY outcome

Timeframe: Up to 26 weeks

Population: All participants as treated, consisting of all participants (Stages 1 and 2) who received study medication. Study terminated before Stage 2 enrollment; no data were collected for Stage 2-specific arms.

The number of participants experiencing an adverse event (AE) was assessed. An AE is any unfavorable and unintended medical occurrence, symptom, or disease witnessed in a participant, regardless of whether or not a causal relationship with the study treatment can be demonstrated. Further, any worsening of a preexisting condition that is temporally associated with the use of the study treatment is also considered an AE.

Outcome measures

Outcome measures
Measure	MK-7622 High Dose - 45 mg (Stage 1) n=119 Participants Single 45 mg MK-7622 capsule once daily, taken orally. Dose escalated as follows: 15 mg MK-7622 once daily for 1 week; 30 mg MK-7622 once daily for 1 week; and 45 mg MK-7622 once daily for the remainder of treatment.	Placebo (Stage 1) n=120 Participants Matching placebo to MK-7622 capsule once daily, taken orally.	Placebo (Stage 2) Matching placebo to MK-7622 capsule once daily, taken orally.	MK-7622 Mid Dose - 15 mg (Stage 2) Single 15 mg MK-7622 capsule once daily, taken orally.	MK-7622 High Dose - 45 mg (Stage 2) Single 45 mg MK-7622 capsule once daily, taken orally. Dose escalated as follows: 15 mg MK-7622 once daily for 1 week; 30 mg MK-7622 once daily for 1 week; and 45 mg MK-7622 once daily for the remainder of treatment.	Placebo (Stage 2) Matching placebo to MK-7622 capsule once daily, taken orally.
Number of Participants Experiencing an Adverse Event (AE)	83 Participants	71 Participants	—	—	—	—

PRIMARY outcome

Timeframe: Up to 24 weeks

The number of participants discontinuing study drug due to an AE was assessed.

Outcome measures

Outcome measures
Measure	MK-7622 High Dose - 45 mg (Stage 1) n=119 Participants Single 45 mg MK-7622 capsule once daily, taken orally. Dose escalated as follows: 15 mg MK-7622 once daily for 1 week; 30 mg MK-7622 once daily for 1 week; and 45 mg MK-7622 once daily for the remainder of treatment.	Placebo (Stage 1) n=120 Participants Matching placebo to MK-7622 capsule once daily, taken orally.	Placebo (Stage 2) Matching placebo to MK-7622 capsule once daily, taken orally.	MK-7622 Mid Dose - 15 mg (Stage 2) Single 15 mg MK-7622 capsule once daily, taken orally.	MK-7622 High Dose - 45 mg (Stage 2) Single 45 mg MK-7622 capsule once daily, taken orally. Dose escalated as follows: 15 mg MK-7622 once daily for 1 week; 30 mg MK-7622 once daily for 1 week; and 45 mg MK-7622 once daily for the remainder of treatment.	Placebo (Stage 2) Matching placebo to MK-7622 capsule once daily, taken orally.
Number of Participants Who Discontinued Study Drug Due to an AE	19 Participants	7 Participants	—	—	—	—

SECONDARY outcome

Timeframe: Baseline and week 24

Population: Per protocol, analysis population was to include all randomized participants (pooled across Stages 1 and 2) receiving ≥1 dose of placebo or MK-7622 - 45 mg, having either a baseline or 24-week ADCS-ADL assessment. As the study was terminated before Stage 2 enrollment, only participants in Stage 1 were analyzed.

Mean change from baseline at week 24 was assessed for ADCS-ADL score. The ADCS-ADL score measures the performance of activities of daily living, calculated from a 24-question survey. For each of the 24 questions, scores range from 0 (no independence) to (depending on the question) either 2 (1 question), 3 (17 questions), 4 (5 questions), or 5 (1 question), with higher scores indicating greater independence in activity performance. Scores from individual questions are summed into a total ADCS-ADL score, with potential total scores ranging from 0 to 78. Lower scores indicate less independence in activity performance and, as a result, greater AD severity. Further, increases in AD severity over time would be reflected by decreases in ADCS-ADL score.

Outcome measures

Outcome measures
Measure	MK-7622 High Dose - 45 mg (Stage 1) n=119 Participants Single 45 mg MK-7622 capsule once daily, taken orally. Dose escalated as follows: 15 mg MK-7622 once daily for 1 week; 30 mg MK-7622 once daily for 1 week; and 45 mg MK-7622 once daily for the remainder of treatment.	Placebo (Stage 1) n=119 Participants Matching placebo to MK-7622 capsule once daily, taken orally.	Placebo (Stage 2) Matching placebo to MK-7622 capsule once daily, taken orally.	MK-7622 Mid Dose - 15 mg (Stage 2) Single 15 mg MK-7622 capsule once daily, taken orally.	MK-7622 High Dose - 45 mg (Stage 2) Single 45 mg MK-7622 capsule once daily, taken orally. Dose escalated as follows: 15 mg MK-7622 once daily for 1 week; 30 mg MK-7622 once daily for 1 week; and 45 mg MK-7622 once daily for the remainder of treatment.	Placebo (Stage 2) Matching placebo to MK-7622 capsule once daily, taken orally.
Change From Baseline in Alzheimer's Disease Cooperative Study-Activities of Daily Living Inventory (ADCS-ADL) at Week 24 (Combining Stage 1 and 2, MK-7622 45 mg Versus Placebo)	-2.66 Score on a Scale Standard Error 0.919	-2.73 Score on a Scale Standard Error 0.853	—	—	—	—

SECONDARY outcome

Timeframe: Baseline and week 12

Population: All randomized participants in Stage 1 receiving ≥1 dose of study medication, having either a baseline or 12-week CCS-3D assessment.

CCS-3D is composed of individual cognitive tests, grouped into 3 domains: 1) episodic memory; 2) executive function; and 3) attention/processing speed. For each cognitive test, a z-score (Z) is calculated at each time point \[Z = (observed value - study population mean at baseline) / study population standard deviation at baseline\]. These individual Zs are first combined into domain-specific Zs, and then into a composite Z, (i.e. CCS-3D). Theoretically, 99.9% of CCS-3D will be ± 3; more positive CCS-3D indicate greater cognitive impairment relative to the total study population at baseline. Further, negative changes in CCS-3D over time indicate improved cognition relative to the total study population at baseline.

Outcome measures

Outcome measures
Measure	MK-7622 High Dose - 45 mg (Stage 1) n=108 Participants Single 45 mg MK-7622 capsule once daily, taken orally. Dose escalated as follows: 15 mg MK-7622 once daily for 1 week; 30 mg MK-7622 once daily for 1 week; and 45 mg MK-7622 once daily for the remainder of treatment.	Placebo (Stage 1) n=110 Participants Matching placebo to MK-7622 capsule once daily, taken orally.	Placebo (Stage 2) Matching placebo to MK-7622 capsule once daily, taken orally.	MK-7622 Mid Dose - 15 mg (Stage 2) Single 15 mg MK-7622 capsule once daily, taken orally.	MK-7622 High Dose - 45 mg (Stage 2) Single 45 mg MK-7622 capsule once daily, taken orally. Dose escalated as follows: 15 mg MK-7622 once daily for 1 week; 30 mg MK-7622 once daily for 1 week; and 45 mg MK-7622 once daily for the remainder of treatment.	Placebo (Stage 2) Matching placebo to MK-7622 capsule once daily, taken orally.
Change From Baseline in Composite Cognition Score-3 Domain (CCS-3D) at Week 12 (Stage 1, MK-7622 45 mg Versus Placebo)	0.13 z-score Standard Error 0.043	0.03 z-score Standard Error 0.042	—	—	—	—

SECONDARY outcome

Timeframe: Baseline and Week 12

Population: Per study protocol, the analysis population was to include only randomized participants in Stage 2 receiving ≥1 dose of placebo, MK-7622 - 15 mg, or MK-7622 - 45 mg, having either a baseline or 12-week CCS-3D assessment. Study terminated before Stage 2 enrollment; no data were collected for this outcome measure.

Outcome measures

Outcome data not reported

Adverse Events

MK-7622 High Dose - 45 mg (Stage 1)

Serious events: 9 serious events

Other events: 42 other events

Deaths: 0 deaths

Placebo (Stage 1)

Serious events: 4 serious events

Other events: 20 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	MK-7622 High Dose - 45 mg (Stage 1) n=119 participants at risk Single 45 mg MK-7622 capsule once daily, taken orally. Dose escalated as follows: 15 mg MK-7622 once daily for 1 week; 30 mg MK-7622 once daily for 1 week; and 45 mg MK-7622 once daily for the remainder of treatment.	Placebo (Stage 1) n=120 participants at risk Matching placebo to MK-7622 capsule once daily, taken orally.
Cardiac disorders Bradycardia	0.84% 1/119 • Number of events 1 • Up to 26 weeks	0.00% 0/120 • Up to 26 weeks
Gastrointestinal disorders Pancreatitis acute	0.00% 0/119 • Up to 26 weeks	0.83% 1/120 • Number of events 1 • Up to 26 weeks
General disorders Fatigue	0.84% 1/119 • Number of events 1 • Up to 26 weeks	0.00% 0/120 • Up to 26 weeks
Infections and infestations Upper respiratory tract infection	0.84% 1/119 • Number of events 1 • Up to 26 weeks	0.00% 0/120 • Up to 26 weeks
Infections and infestations Urinary tract infection	0.00% 0/119 • Up to 26 weeks	1.7% 2/120 • Number of events 2 • Up to 26 weeks
Injury, poisoning and procedural complications Eye injury	0.00% 0/119 • Up to 26 weeks	0.83% 1/120 • Number of events 1 • Up to 26 weeks
Injury, poisoning and procedural complications Fall	0.00% 0/119 • Up to 26 weeks	1.7% 2/120 • Number of events 2 • Up to 26 weeks
Metabolism and nutrition disorders Dehydration	0.00% 0/119 • Up to 26 weeks	0.83% 1/120 • Number of events 1 • Up to 26 weeks
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Cholangiocarcinoma	0.84% 1/119 • Number of events 1 • Up to 26 weeks	0.00% 0/120 • Up to 26 weeks
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lung neoplasm malignant	0.84% 1/119 • Number of events 1 • Up to 26 weeks	0.00% 0/120 • Up to 26 weeks
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Prostate cancer	0.84% 1/119 • Number of events 1 • Up to 26 weeks	0.00% 0/120 • Up to 26 weeks
Nervous system disorders Ischaemic stroke	0.84% 1/119 • Number of events 1 • Up to 26 weeks	0.00% 0/120 • Up to 26 weeks
Nervous system disorders Normal pressure hydrocephalus	0.84% 1/119 • Number of events 1 • Up to 26 weeks	0.00% 0/120 • Up to 26 weeks
Nervous system disorders Syncope	0.00% 0/119 • Up to 26 weeks	0.83% 1/120 • Number of events 1 • Up to 26 weeks
Psychiatric disorders Bipolar I disorder	0.84% 1/119 • Number of events 1 • Up to 26 weeks	0.00% 0/120 • Up to 26 weeks
Psychiatric disorders Mental status changes	0.84% 1/119 • Number of events 1 • Up to 26 weeks	0.00% 0/120 • Up to 26 weeks
Reproductive system and breast disorders Benign prostatic hyperplasia	0.84% 1/119 • Number of events 1 • Up to 26 weeks	0.00% 0/120 • Up to 26 weeks

Other adverse events

Other adverse events
Measure	MK-7622 High Dose - 45 mg (Stage 1) n=119 participants at risk Single 45 mg MK-7622 capsule once daily, taken orally. Dose escalated as follows: 15 mg MK-7622 once daily for 1 week; 30 mg MK-7622 once daily for 1 week; and 45 mg MK-7622 once daily for the remainder of treatment.	Placebo (Stage 1) n=120 participants at risk Matching placebo to MK-7622 capsule once daily, taken orally.
Gastrointestinal disorders Diarrhoea	15.1% 18/119 • Number of events 19 • Up to 26 weeks	5.8% 7/120 • Number of events 9 • Up to 26 weeks
Infections and infestations Urinary tract infection	5.0% 6/119 • Number of events 7 • Up to 26 weeks	4.2% 5/120 • Number of events 6 • Up to 26 weeks
Investigations Weight decreased	5.0% 6/119 • Number of events 6 • Up to 26 weeks	1.7% 2/120 • Number of events 2 • Up to 26 weeks
Nervous system disorders Headache	9.2% 11/119 • Number of events 12 • Up to 26 weeks	5.0% 6/120 • Number of events 7 • Up to 26 weeks
Renal and urinary disorders Urinary incontinence	5.0% 6/119 • Number of events 6 • Up to 26 weeks	0.00% 0/120 • Up to 26 weeks
Respiratory, thoracic and mediastinal disorders Rhinorrhoea	5.9% 7/119 • Number of events 7 • Up to 26 weeks	0.83% 1/120 • Number of events 1 • Up to 26 weeks

Additional Information

Senior Vice President, Global Clinical Development

Merck Sharp & Dohme Corp.

Phone: 1-800-672-6372

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The Sponsor must have the opportunity to review all proposed abstracts, manuscripts or presentations regarding this trial 45 days prior to submission for publication/presentation. Any information identified by the Sponsor as confidential must be deleted prior to submission; this confidentiality does not include efficacy and safety results. Sponsor review can be expedited to meet publication timelines.
Publication restrictions are in place

Restriction type: OTHER