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| ID | Type | Description | Link |
|---|---|---|---|
| 2009_592 |
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This study will assess the effect of combined treatment with MK0893 plus propranolol versus placebo plus propranolol on hypoglycemia.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Propanolol + Placebo > Propanolol + MK0893 | Experimental | Participants received propanolol for 7 weeks. On Day -1 of Period 1 (Study Visit 6), single dose MK0893-matched placebo was added and propanolol was continued. After Period 1, participants underwent a 3-week wash-out while continuing to receive propanolol. Following the washout, participants were treated with a single dose of MK0893 on Day 21 (Visit 8). |
|
| Propanolol + MK0893 > Propanolol + Placebo | Placebo Comparator | Participants received propanolol for 7 weeks. On Day -1 of Period 1 (Study Visit 6), single dose MK0893 was added and propanolol was continued. After Period 1, participants underwent a 3-week wash-out while continuing to receive propanolol. Following the washout, participants were treated with a single dose of MK0893-matched placebo on Day 21 (Visit 8). |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| MK0893 | Drug | Single dose of MK0893 1000 mg (ten 100 mg tablets) |
|
| Measure | Description | Time Frame |
|---|---|---|
| Recovery Time (Rt[65] From Insulin-induced Hypoglycemia | Rt(65) defined as the time to recover from hypoglycemia (blood glucose level of 50 mg/dL) to an arterialized venous blood glucose of 65 mg/dL. At t= -60 minutes on the morning of Day 1 (Visit 6) or Day 22 (Visit 8), a hypoglycemic clamp was used via an increased insulin infusion rate to achieve blood glucose concentrations of 50 mg/dL (2.8 mmol/L) within ~30-90 minutes. At the end of the 30-minute hypoglycemic clamp interval, insulin and glucose infusions were terminated, and the time to recover from hypoglycemia to 65 mg/dL Rt(65) was determined. Rt(65) was followed up to 270 minutes | From the time of hypoglycemic clamp (t=0 minutes) through 270 minutes |
| Measure | Description | Time Frame |
|---|---|---|
| Maximum Plasma Concentration (Cmax) and Concentration Average Over 8-12 Hours (C[Ave] 8-12 hr) Post Single Dose MK0893 | Cmax was the maximum or "peak" concentration of MK0893 observed after its administration. Approximate C(ave 8-12) was the MK0893 concentration average over 8-12 hours post-dose and was computed as the Area Under the Curve over 8-12 hours post-dose (AUC [8-12]) ÷ 4 | From time of MK0893 administration through 24 hours post-dose |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Medical Monitor | Merck Sharp & Dohme LLC | Study Director |
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| ID | Title | Description |
|---|---|---|
| FG000 | Propanolol + MK0893 / Propanolol + Placebo | After a 4 week wash-out period with a 4-week propanolol run-on, single dose MK0893 was added on Day -1 of Period 1 (Study Visit 6) and propanolol was continued. After Period 1, participants underwent a 3-week wash-out while continuing to receive propanolol alone. Following the washout, participants were treated with a single dose of MK0893-matched placebo on Day 21 (Visit 8) while continuing on propanolol. |
| FG001 | Propanolol + Placebo / Propanolol + MK0893 | After a 4 week wash-out period with a 4-week propanolol run-on, MK0893-matched placebo was added on Day -1 of Period 1 (Study Visit 6) and propanolol was continued. After Period 1, participants underwent a 3-week wash-out while continuing to receive propanolol alone. Following the washout, participants were treated with a single dose of MK0893 on Day 21 (Visit 8) while continuing on propanolol. |
| FG002 | Propanolol Alone | Participants received treatment with propanolol alone during a 4 week run-on before the 1st clamp procedure at Visit 6, and during a 3 week washout between clamp procedures at Visits 6 (Period 1) and 8 (Period 2). Overall, participants were treated with propranolol for approximately 7 weeks (from propranol titration through Visit 8 clamp procedures). |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Pre-study Washout/Propanolol Run-in |
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| Period 1 |
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| Post-clamp Washout |
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| Period 2 |
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| ID | Title | Description |
|---|---|---|
| BG000 | MK0893 + Propanolol | Participants received a single dose of MK0893 added to a background of propanolol at either Visit 6 (Day -1) or Visit 8 (Day 21). |
| BG001 | Placebo + Propanolol |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Recovery Time (Rt[65] From Insulin-induced Hypoglycemia | Rt(65) defined as the time to recover from hypoglycemia (blood glucose level of 50 mg/dL) to an arterialized venous blood glucose of 65 mg/dL. At t= -60 minutes on the morning of Day 1 (Visit 6) or Day 22 (Visit 8), a hypoglycemic clamp was used via an increased insulin infusion rate to achieve blood glucose concentrations of 50 mg/dL (2.8 mmol/L) within ~30-90 minutes. At the end of the 30-minute hypoglycemic clamp interval, insulin and glucose infusions were terminated, and the time to recover from hypoglycemia to 65 mg/dL Rt(65) was determined. Rt(65) was followed up to 270 minutes | 21 participants who received MK0893 + Propanolol while on study had data available, and 17 participants who received Placebo + Propanolol while on study had data available | Posted | Least Squares Mean | 95% Confidence Interval | minutes | From the time of hypoglycemic clamp (t=0 minutes) through 270 minutes |
|
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | MK0893 + Propanolol | Participants received a single dose of MK0893 added to a background of propanolol at either Visit 6 (Day -1) or Visit 8 (Day 21). |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Iron Deficiency Anaemia | Blood and lymphatic system disorders | MedDRA 14.0 |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Senior Vice President, Global Clinical Development | Merck Sharp & Dohme Corp | 1-800-672-6372 | ClinicalTrialsDisclosure@merck.com |
| ID | Term |
|---|---|
| D003924 | Diabetes Mellitus, Type 2 |
| ID | Term |
|---|---|
| D003920 | Diabetes Mellitus |
| D044882 | Glucose Metabolism Disorders |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
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| ID | Term |
|---|---|
| C575263 | N-((4-(1-(3-(3,5-dichlorophenyl)-5-(6-methoxynaphthalen-2-yl)-1H-pyrazol-1-yl)ethyl)phenyl)carbonyl)-beta-alanine |
| D011433 | Propranolol |
| ID | Term |
|---|---|
| D050198 | Phenoxypropanolamines |
| D011412 | Propanolamines |
| D000605 | Amino Alcohols |
| D000438 | Alcohols |
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| MK0893-matched Placebo | Drug | Single dose of placebo to MK0893 (ten tablets) |
|
| Propranolol Hydrochloride (HCL) | Drug | Propranolol tablets titrated up to 80 mg three times daily over a four week period. Total treatment was approximately 7 weeks. |
|
| Plasma Concentration at 32 Hours (C[32hr]) Post Single Dose MK0893 | Plasma concentration of single dose MK0893 was measured from time of administration to 24 hours post-dose and extrapolated out to 32 hours post-dose using the plasma concentration vs. time curve | From time of MK0893 administration through estimated 32 hours post-dose |
| Number of Participants With An Adverse Event (AE) | An AE was defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the Sponsor's product, whether or not considered related to the use of the product. This also included any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition which is temporally associated with the use of the Sponsor's product. | From time of administration of study treatment through end of Post-Study (up to 21 days after administration of last dose of study treatment). |
| Number of Participants Who Discontinued Study Treatment Due To AEs | An AE was defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the Sponsor's product, whether or not considered related to the use of the product. This also included any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition which is temporally associated with the use of the Sponsor's product. | From time of first administration of study treatment to time of last administration of study treatment (up to Day 21) |
| NOT COMPLETED |
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| NOT COMPLETED |
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| NOT COMPLETED |
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Participants received a single dose of MK0893-matched placebo added to a background of propanolol at either Visit 6 (Day -1) or Visit 8 (Day 21).
| BG002 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
Participants received a single dose of MK0893 added to a background of propanolol at either Visit 6 (Day -1) or Visit 8 (Day 21). |
| OG001 | Placebo + Propanolol | Participants received a single dose of MK0893 added to a background of propanolol at either Visit 6 (Day -1) or Visit 8 (Day 21). |
|
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| Secondary | Maximum Plasma Concentration (Cmax) and Concentration Average Over 8-12 Hours (C[Ave] 8-12 hr) Post Single Dose MK0893 | Cmax was the maximum or "peak" concentration of MK0893 observed after its administration. Approximate C(ave 8-12) was the MK0893 concentration average over 8-12 hours post-dose and was computed as the Area Under the Curve over 8-12 hours post-dose (AUC [8-12]) ÷ 4 | Data from the first 15 participants who completed the study were used for the pharmacokinetic analysis. | Posted | Mean | Standard Deviation | uM | From time of MK0893 administration through 24 hours post-dose |
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|
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| Secondary | Plasma Concentration at 32 Hours (C[32hr]) Post Single Dose MK0893 | Plasma concentration of single dose MK0893 was measured from time of administration to 24 hours post-dose and extrapolated out to 32 hours post-dose using the plasma concentration vs. time curve | Data from the first 15 participants who completed the study were used for the pharmacokinetic analysis. | Posted | Mean | Standard Deviation | nM | From time of MK0893 administration through estimated 32 hours post-dose |
|
|
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| Secondary | Number of Participants With An Adverse Event (AE) | An AE was defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the Sponsor's product, whether or not considered related to the use of the product. This also included any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition which is temporally associated with the use of the Sponsor's product. | All treated participants | Posted | Number | participants | From time of administration of study treatment through end of Post-Study (up to 21 days after administration of last dose of study treatment). |
|
|
|
| Secondary | Number of Participants Who Discontinued Study Treatment Due To AEs | An AE was defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the Sponsor's product, whether or not considered related to the use of the product. This also included any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition which is temporally associated with the use of the Sponsor's product. | All treated participants | Posted | Number | participants | From time of first administration of study treatment to time of last administration of study treatment (up to Day 21) |
|
|
|
| 0 |
| 22 |
| 10 |
| 22 |
| EG001 | Placebo + Propanolol | Participants received a single dose of MK0893-matched placebo added to a background of propanolol at either Visit 6 (Day -1) or Visit 8 (Day 21). | 0 | 22 | 4 | 22 |
| EG002 | Propanolol Alone | Participants received treatment with propanolol alone during a 4 week washout before the 1st clamp procedure at Visit 6, and during a 3 week washout between clamp procedures at Visits 6 (Period 1) and 8 (Period 2). Overall, participants were treated with propranolol for approximately 7 weeks (from propranolol titration through Visit 8 clamp procedures). | 0 | 22 | 9 | 22 |
| Arrhythmia Supraventricular | Cardiac disorders | MedDRA 14.0 |
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| Vision Blurred | Eye disorders | MedDRA 14.0 |
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| Abdominal Pain | Gastrointestinal disorders | MedDRA 14.0 |
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| Diarrhoea | Gastrointestinal disorders | MedDRA 14.0 |
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| Nausea | Gastrointestinal disorders | MedDRA 14.0 |
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| Chest Discomfort | General disorders | MedDRA 14.0 |
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| Chest Pain | General disorders | MedDRA 14.0 |
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| Fatigue | General disorders | MedDRA 14.0 |
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| Feeling Hot | General disorders | MedDRA 14.0 |
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| Gastroenteritis Viral | Infections and infestations | MedDRA 14.0 |
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| Wrist Fracture | Injury, poisoning and procedural complications | MedDRA 14.0 |
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| Haematocrit Decreased | Investigations | MedDRA 14.0 |
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| Haemoglobin Decreased | Investigations | MedDRA 14.0 |
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| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA 14.0 |
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| Joint Effusion | Musculoskeletal and connective tissue disorders | MedDRA 14.0 |
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| Dizziness | Nervous system disorders | MedDRA 14.0 |
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| Dizziness Postural | Nervous system disorders | MedDRA 14.0 |
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| Headache | Nervous system disorders | MedDRA 14.0 |
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| Somnolence | Nervous system disorders | MedDRA 14.0 |
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| Insomnia | Psychiatric disorders | MedDRA 14.0 |
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| Hyperhidrosis | Skin and subcutaneous tissue disorders | MedDRA 14.0 |
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The SPONSOR must have the opportunity to review all proposed abstracts, manuscripts, or presentations regarding this study 60 days prior to submission for publication/presentation. Any information identified by the SPONSOR as confidential must be deleted prior to submission. SPONSOR review can be expedited to meet publication guidelines.
| D004700 | Endocrine System Diseases |
| D009930 |
| Organic Chemicals |
| D020005 | Propanols |
| D000588 | Amines |
| D009281 | Naphthalenes |
| D011084 | Polycyclic Aromatic Hydrocarbons |
| D006841 | Hydrocarbons, Aromatic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D011083 | Polycyclic Compounds |