Efficacy and Safety of MK-7622 as Adjunct Therapy in Participants With Alzheimer's Disease (MK-7622-012)

• ClinicalTrials.gov Identifier: NCT01852110
• Recruitment Status: Terminated
• First Posted: May 13, 2013
• Results First Posted: February 7, 2018
• Last Update Posted: September 18, 2018
• Sponsor: Merck Sharp & Dohme LLC
• Information provided by (Responsible Party): Merck Sharp & Dohme LLC

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Triple (Participant, Care Provider, Investigator); Primary Purpose: Treatment
• Condition: Alzheimer's Disease
• Interventions: Drug: MK-7622; Drug: Placebo; Drug: AChEI
• Enrollment: 240

Participant Flow

Recruitment Details	Number of Participants Screened: 505 Number of Participants Randomized: 240
Pre-assignment Details	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).

Arm/Group Title	MK-7622 High Dose - 45 mg (Stage 1)	Placebo (Stage 1)	MK-7622 Low Dose - 5 mg (Stage 2)	MK-7622 Mid Dose - 15 mg (Stage 2)	MK-7622 High Dose - 45 mg (Stage 2)	Placebo (Stage 2)
Arm/Group Description	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.	Matching placebo to MK-7622 capsule once daily, taken orally.	Single 5 mg MK-7622 capsule once daily, taken orally.	Single 15 mg MK-7622 capsule once daily, taken orally.	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.	Matching placebo to MK-7622 capsule once daily, taken orally.
Period Title: Overall Study
Started	120	120	0 [1]	0 [1]	0 [1]	0 [1]
Treated	119	120	0	0	0	0
Completed	70	74	0 [1]	0 [1]	0 [1]	0 [1]
Not Completed	50	46	0	0	0	0
Reason Not Completed
Adverse Event	12	5	0	0	0	0
Lost to Follow-up	1	3	0	0	0	0
Non-compliance with Study Drug	2	1	0	0	0	0
Physician Decision	1	0	0	0	0	0
Protocol Violation	0	1	0	0	0	0
Study Terminated by Sponsor	30	32	0	0	0	0
Withdrawal by Subject	4	4	0	0	0	0
[1] Study terminated prior to participant recruitment for Stage 2

Baseline Characteristics

Arm/Group Title		MK-7622 High Dose - 45 mg (Stage 1)	Placebo (Stage 1)	Total
Arm/Group Description		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.	Matching placebo to MK-7622 capsule once daily, taken orally.	Total of all reporting groups
Overall Number of Baseline Participants		119	120	239
Baseline Analysis Population Description		Includes only participants in Stage 1 who were both randomized (i.e. started) and treated. In stage 1: MK-7622 High Dose - 45 mg: of the randomized participants (n=120), all but 1 randomized participant received study treatment (n=119). Placebo: Of the randomized participants (n=120), all received study treatment (n=120).
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	119 participants	120 participants	239 participants
		72.5 (7.1)	71.7 (8.3)	72.1 (7.7)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	119 participants	120 participants	239 participants
	Female	61 51.3%	68 56.7%	129 54.0%
	Male	58 48.7%	52 43.3%	110 46.0%
11-item Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog11) Score [1] [2]; Mean (Standard Deviation); Unit of measure: Score on a Scale
	Number Analyzed	119 participants	120 participants	239 participants
		21.8 (7.05)	23.6 (8.73)	22.7 (7.95)
		[1] Measure Description: 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 (range: 0-70). Higher total scores indicate greater cognitive impairment.; [2] Measure Analysis Population Description: 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 [1] [2]; Mean (Standard Deviation); Unit of measure: Score on a Scale
	Number Analyzed	119 participants	119 participants	238 participants
		60.7 (11.18)	59.4 (11.89)	59.9 (11.72)
		[1] Measure Description: 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.; [2] Measure Analysis Population Description: Includes only randomized participants receiving ≥1 dose of study medication, having a baseline ADCS-ADL assessment.
Composite Cognition Score-3 Domain (CCS-3D) [1] [2]; Mean (Standard Deviation); Unit of measure: Z-score
	Number Analyzed	108 participants	110 participants	218 participants
		-0.11 (0.739)	0.02 (0.816)	-0.039 (0.776)
		[1] Measure Description: 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.; [2] Measure Analysis Population Description: Includes only randomized participants receiving ≥1 dose of study medication, having a baseline CCS-3D assessment.

Outcome Measures

1. Primary Outcome

Title	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)
Description	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.
Time Frame	Baseline and week 12

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	MK-7622 High Dose - 45 mg (Stage 1)	Placebo (Stage 1)
Arm/Group Description:	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.	Matching placebo to MK-7622 capsule once daily, taken orally.
Overall Number of Participants Analyzed	119	120
Mean (Standard Error); Unit of Measure: Score on a Scale
	0.39 (0.440)	0.21 (0.416)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	MK-7622 High Dose - 45 mg (Stage 1), Placebo (Stage 1)
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.7623
	Comments	[Not Specified]
	Method	Constrained Longitudinal Data Analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.18
	Confidence Interval	(2-Sided) 95%; -1.00 to 1.37
	Estimation Comments	[Not Specified]

2. Primary Outcome

Title	Change From Baseline in ADAS-Cog11 Score at Week 12 (Stage 2, MK-7622 45 mg and 15 mg Versus Placebo)
Description	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.
Time Frame	Baseline and week 12

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	MK-7622 Mid Dose - 15 mg (Stage 2)	MK-7622 High Dose - 45 mg (Stage 2)	Placebo (Stage 2)
Arm/Group Description:	Single 15 mg MK-7622 capsule once daily, taken orally.	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.	Matching placebo to MK-7622 capsule once daily, taken orally.
Overall Number of Participants Analyzed	0	0	0

No data displayed because Outcome Measure has zero total analyzed.

3. Primary Outcome

Title	Number of Participants Experiencing an Adverse Event (AE)
Description	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.
Time Frame	Up to 26 weeks

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	MK-7622 High Dose - 45 mg (Stage 1)	Placebo (Stage 1)	MK-7622 Low Dose - 5 mg (Stage 2)	MK-7622 Mid Dose - 15 mg (Stage 2)	MK-7622 High Dose - 45 mg (Stage 2)	Placebo (Stage 2)
Arm/Group Description:	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.	Matching placebo to MK-7622 capsule once daily, taken orally.	Single 5 mg MK-7622 capsule once daily, taken orally.	Single 15 mg MK-7622 capsule once daily, taken orally.	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.	Matching placebo to MK-7622 capsule once daily, taken orally.
Overall Number of Participants Analyzed	119	120	0	0	0	0
Measure Type: Count of Participants; Unit of Measure: Participants
	83 69.7%	71 59.2%

4. Primary Outcome

Title	Number of Participants Who Discontinued Study Drug Due to an AE
Description	The number of participants discontinuing study drug due to an AE was assessed.
Time Frame	Up to 24 weeks

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	MK-7622 High Dose - 45 mg (Stage 1)	Placebo (Stage 1)	MK-7622 Low Dose - 5 mg (Stage 2)	MK-7622 Mid Dose - 15 mg (Stage 2)	MK-7622 High Dose - 45 mg (Stage 2)	Placebo (Stage 2)
Arm/Group Description:	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.	Matching placebo to MK-7622 capsule once daily, taken orally.	Single 5 mg MK-7622 capsule once daily, taken orally, for 24 weeks	Single 15 mg MK-7622 capsule once daily, taken orally.	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.	Matching placebo to MK-7622 capsule once daily, taken orally.
Overall Number of Participants Analyzed	119	120	0	0	0	0
Measure Type: Count of Participants; Unit of Measure: Participants
	19 16.0%	7 5.8%

5. Secondary Outcome

Title	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)
Description	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.
Time Frame	Baseline and week 24

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	MK-7622 High Dose - 45 mg (Stage 1)	Placebo (Stage 1)
Arm/Group Description:	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.	Matching placebo to MK-7622 capsule once daily, taken orally.
Overall Number of Participants Analyzed	119	119
Mean (Standard Error); Unit of Measure: Score on a Scale
	-2.66 (0.919)	-2.73 (0.853)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	MK-7622 High Dose - 45 mg (Stage 1), Placebo (Stage 1)
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.9604
	Comments	[Not Specified]
	Method	Constrained Longitudinal Data Analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.06
	Confidence Interval	(2-Sided) 95%; -2.42 to 2.54
	Estimation Comments	[Not Specified]

6. Secondary Outcome

Title	Change From Baseline in Composite Cognition Score-3 Domain (CCS-3D) at Week 12 (Stage 1, MK-7622 45 mg Versus Placebo)
Description	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.
Time Frame	Baseline and week 12

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	MK-7622 High Dose - 45 mg (Stage 1)	Placebo (Stage 1)
Arm/Group Description:	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.	Matching placebo to MK-7622 capsule once daily, taken orally.
Overall Number of Participants Analyzed	108	110
Mean (Standard Error); Unit of Measure: z-score
	0.13 (0.043)	0.03 (0.042)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	MK-7622 High Dose - 45 mg (Stage 1), Placebo (Stage 1)
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.0829
	Comments	[Not Specified]
	Method	Constrained Longitudinal Data Analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.10
	Confidence Interval	(2-Sided) 95%; -0.01 to 0.22
	Estimation Comments	[Not Specified]

7. Secondary Outcome

Title	Change From Baseline in CCS-3D at Week 12 (Stage 2, MK-7622 45 mg and 15 mg Versus Placebo)
Description	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.
Time Frame	Baseline and Week 12

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	MK-7622 Mid Dose - 15 mg (Stage 2)	MK-7622 High Dose - 45 mg (Stage 2)	Placebo (Stage 2)
Arm/Group Description:	Single 15 mg MK-7622 capsule once daily, taken orally.	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.	Matching placebo to MK-7622 capsule once daily, taken orally.
Overall Number of Participants Analyzed	0	0	0

No data displayed because Outcome Measure has zero total analyzed.

Adverse Events

Time Frame	Up to 26 weeks
Adverse Event Reporting Description	[Not Specified]
Arm/Group Title	MK-7622 High Dose - 45 mg (Stage 1)		Placebo (Stage 1)
Arm/Group Description	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.		Matching placebo to MK-7622 capsule once daily, taken orally.
All-Cause Mortality
	MK-7622 High Dose - 45 mg (Stage 1)		Placebo (Stage 1)
	Affected / at Risk (%)		Affected / at Risk (%)
Total	--/--		--/--
Serious Adverse Events
	MK-7622 High Dose - 45 mg (Stage 1)		Placebo (Stage 1)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	9/119 (7.56%)		4/120 (3.33%)
Cardiac disorders
Bradycardia † 1	1/119 (0.84%)	1	0/120 (0.00%)	0
Gastrointestinal disorders
Pancreatitis acute † 1	0/119 (0.00%)	0	1/120 (0.83%)	1
General disorders
Fatigue † 1	1/119 (0.84%)	1	0/120 (0.00%)	0
Infections and infestations
Upper respiratory tract infection † 1	1/119 (0.84%)	1	0/120 (0.00%)	0
Urinary tract infection † 1	0/119 (0.00%)	0	2/120 (1.67%)	2
Injury, poisoning and procedural complications
Eye injury † 1	0/119 (0.00%)	0	1/120 (0.83%)	1
Fall † 1	0/119 (0.00%)	0	2/120 (1.67%)	2
Metabolism and nutrition disorders
Dehydration † 1	0/119 (0.00%)	0	1/120 (0.83%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Cholangiocarcinoma † 1	1/119 (0.84%)	1	0/120 (0.00%)	0
Lung neoplasm malignant † 1	1/119 (0.84%)	1	0/120 (0.00%)	0
Prostate cancer † 1	1/119 (0.84%)	1	0/120 (0.00%)	0
Nervous system disorders
Ischaemic stroke † 1	1/119 (0.84%)	1	0/120 (0.00%)	0
Normal pressure hydrocephalus † 1	1/119 (0.84%)	1	0/120 (0.00%)	0
Syncope † 1	0/119 (0.00%)	0	1/120 (0.83%)	1
Psychiatric disorders
Bipolar I disorder † 1	1/119 (0.84%)	1	0/120 (0.00%)	0
Mental status changes † 1	1/119 (0.84%)	1	0/120 (0.00%)	0
Reproductive system and breast disorders
Benign prostatic hyperplasia † 1	1/119 (0.84%)	1	0/120 (0.00%)	0
† Indicates events were collected by systematic assessment; 1 Term from vocabulary, MedDRA 19.0
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	MK-7622 High Dose - 45 mg (Stage 1)		Placebo (Stage 1)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	42/119 (35.29%)		20/120 (16.67%)
Gastrointestinal disorders
Diarrhoea † 1	18/119 (15.13%)	19	7/120 (5.83%)	9
Infections and infestations
Urinary tract infection † 1	6/119 (5.04%)	7	5/120 (4.17%)	6
Investigations
Weight decreased † 1	6/119 (5.04%)	6	2/120 (1.67%)	2
Nervous system disorders
Headache † 1	11/119 (9.24%)	12	6/120 (5.00%)	7
Renal and urinary disorders
Urinary incontinence † 1	6/119 (5.04%)	6	0/120 (0.00%)	0
Respiratory, thoracic and mediastinal disorders
Rhinorrhoea † 1	7/119 (5.88%)	7	1/120 (0.83%)	1
† Indicates events were collected by systematic assessment; 1 Term from vocabulary, MedDRA 19.0

Limitations and Caveats

Stage 1 Interim analysis of efficacy met the clinical criteria for early trial termination (futility). As a result, the trial was terminated at Stage 1 and did not proceed to Stage 2.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

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.

Results Point of Contact

• Name/Title: Senior Vice President, Global Clinical Development
• Organization: Merck Sharp & Dohme Corp.
• Phone: 1-800-672-6372
• EMail: ClinicalTrialsDisclosure@merck.com

Publications of Results:

Voss T, Li J, Cummings J, Farlow M, Assaid C, Froman S, Leibensperger H, Snow-Adami L, McMahon KB, Egan M, Michelson D. Randomized, controlled, proof-of-concept trial of MK-7622 in Alzheimer's disease. Alzheimers Dement (N Y). 2018 Apr 26;4:173-181. doi: 10.1016/j.trci.2018.03.004. eCollection 2018.

• Responsible Party: Merck Sharp & Dohme LLC
• ClinicalTrials.gov Identifier: NCT01852110
• Other Study ID Numbers: 7622-012; 2013-000937-11 ( EudraCT Number ); MK-7622-012 ( Other Identifier: Merck Protocol Number )
• First Submitted: May 8, 2013
• First Posted: May 13, 2013
• Results First Submitted: January 8, 2018
• Results First Posted: February 7, 2018
• Last Update Posted: September 18, 2018