Trial Outcomes & Findings for A Clinical Trial to Assess the Long Term Safety and Tolerability of MK-0653C in Japanese Participants With Hypercholesterolemia (MK-0653C-384) (NCT NCT02460159)

Last Updated: 2024-05-16

Results Overview

An AE was defined as any untoward medical occurrence in a subject which does not necessarily have a causal relationship with the treatment. An AE was any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with use of a medicinal product, whether or not considered related to the medicinal product. The percentage of participants that reported at least 1 AE was summarized.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

135 participants

Primary outcome timeframe

up to 54 Weeks

Results posted on

2024-05-16

Participant Flow

Participant milestones

Participant milestones
Measure	EZ 10 mg/Atorva 10 mg FDC One ezetimibe (EZ) 10 mg/atorvastatin (Atorva) 10 mg fixed-dose combination (FDC) tablet orally with food once daily for 52 weeks.	EZ 10 mg/Atorva 20 mg FDC One EZ 10 mg/Atorva 20 mg fixed -dose combination (FDC) tablet orally with food once daily for 52 weeks.
Overall Study STARTED	117	18
Overall Study COMPLETED	111	17
Overall Study NOT COMPLETED	6	1

Reasons for withdrawal

Reasons for withdrawal
Measure	EZ 10 mg/Atorva 10 mg FDC One ezetimibe (EZ) 10 mg/atorvastatin (Atorva) 10 mg fixed-dose combination (FDC) tablet orally with food once daily for 52 weeks.	EZ 10 mg/Atorva 20 mg FDC One EZ 10 mg/Atorva 20 mg fixed -dose combination (FDC) tablet orally with food once daily for 52 weeks.
Overall Study Adverse Event	4	1
Overall Study Withdrawal by Subject	2	0

Baseline Characteristics

A Clinical Trial to Assess the Long Term Safety and Tolerability of MK-0653C in Japanese Participants With Hypercholesterolemia (MK-0653C-384)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	EZ 10 mg/Atorva 10 mg FDC n=117 Participants One ezetimibe (EZ) 10 mg/atorvastatin (Atorva) 10 mg fixed-dose combination (FDC) tablet orally with food once daily for 52 weeks.	EZ 10 mg/Atorva 20 mg FDC n=18 Participants One EZ 10 mg/Atorva 20 mg fixed -dose combination (FDC) tablet orally with food once daily for 52 weeks.	Total n=135 Participants Total of all reporting groups
Age, Continuous	57.8 years STANDARD_DEVIATION 12.6 • n=5 Participants	61.6 years STANDARD_DEVIATION 10.9 • n=7 Participants	58.3 years STANDARD_DEVIATION 12.4 • n=5 Participants
Sex: Female, Male Female	48 Participants n=5 Participants	6 Participants n=7 Participants	54 Participants n=5 Participants
Sex: Female, Male Male	69 Participants n=5 Participants	12 Participants n=7 Participants	81 Participants n=5 Participants

PRIMARY outcome

Timeframe: up to 54 Weeks

Population: All participants that received at least 1 dose of study drug and had available data for endpoint.

Outcome measures

Outcome measures
Measure	EZ 10 mg/Atorva 10 mg FDC n=117 Participants One ezetimibe (EZ) 10 mg/atorvastatin (Atorva) 10 mg fixed-dose combination (FDC) tablet orally with food once daily for 52 weeks.	EZ 10 mg/Atorva 20 mg FDC n=18 Participants One EZ 10 mg/Atorva 20 mg fixed -dose combination (FDC) tablet orally with food once daily for 52 weeks.
Percentage of Participants Who Experience 1 or More Adverse Event (AE)	82.9 Percentage of Participants	88.9 Percentage of Participants

PRIMARY outcome

Timeframe: up to 54 weeks

Population: All participants that received at least 1 dose of study drug and had available data for endpoint.

Gastrointestinal-related AEs included all preferred terms within system organ class of Gastrointestinal Disorders except Chapped Lips and Toothache.

Outcome measures

Outcome measures
Measure	EZ 10 mg/Atorva 10 mg FDC n=117 Participants One ezetimibe (EZ) 10 mg/atorvastatin (Atorva) 10 mg fixed-dose combination (FDC) tablet orally with food once daily for 52 weeks.	EZ 10 mg/Atorva 20 mg FDC n=18 Participants One EZ 10 mg/Atorva 20 mg fixed -dose combination (FDC) tablet orally with food once daily for 52 weeks.
Percentage of Participants Who Experience 1 or More Gastrointestinal-related AEs	30.8 Percentage of participants	11.1 Percentage of participants

PRIMARY outcome

Timeframe: up to 54 weeks

Population: All participants that received at least 1 dose of study drug and had available data for outcome.

Gallbladder-related AEs included Bile Duct Obstruction, Bile Duct Stone, Bile Duct Stenosis, Biliary Colic, Cholangitis, Cholecystectomy, Cholecystitis, Cholelithiasis, Gallbladder Disorder, Gallbladder Perforation, Hepatic Pain, and Hydrocholecystis.

Outcome measures

Outcome measures
Measure	EZ 10 mg/Atorva 10 mg FDC n=117 Participants One ezetimibe (EZ) 10 mg/atorvastatin (Atorva) 10 mg fixed-dose combination (FDC) tablet orally with food once daily for 52 weeks.	EZ 10 mg/Atorva 20 mg FDC n=18 Participants One EZ 10 mg/Atorva 20 mg fixed -dose combination (FDC) tablet orally with food once daily for 52 weeks.
Percentage of Participants Who Experience 1 or More Gallbladder-related AEs	0.0 Percentage of Participants	0.0 Percentage of Participants

PRIMARY outcome

Timeframe: up to 54 weeks

Population: All participants that received at least 1 dose of study drug and had available data for endpoint.

Allergic Reaction or Rash AEs included Allergy to Arthropod Sting, Anaphylactoid Reaction, Anaphylactic Reaction, Anaphylatic Shock, Anaphylactoid Shock, Angioedema, Conjunctivitis Allergic, Contrast Media Reaction, Dermatitis, Dermatitis Allergic, Dermatitis Atopic, Dermatitis Bullous, Dermatitis Contact, Dermatitis Psoriasiform, Drug Hypersensitivity, Eczema, Eosinophila, Erythema, Eye Allergy, Face Oedema, Hypersensitivity, Mechanical Urticaria, Palmar Erythema, Periorbital Oedema, Photodermatosis, Photosensitivity Allergic reaction, Photosensitivity Reaction, Pigmentation Disorder, Pruritus, Pruritus Generalised, Rash, Rash Erythematous, Rash Follicular, Rash Generalised, Rash Maculo-Papular, Rash Papulosquamous, Rash Pruritic, Rash Pustular, Rash Vesicular, Rhinitis, Rhinitis Allergic, Rosacea, Skin Exfoliation, Skin Disorder, Skin Hyperpigmentation, Skin Lesion, Skin Mass, Skin Ulcer, Subcutaneous Nodule, Swelling Face, Systemic Lupus Erythematosus Rash, Urticaria.

Outcome measures

Outcome measures
Measure	EZ 10 mg/Atorva 10 mg FDC n=117 Participants One ezetimibe (EZ) 10 mg/atorvastatin (Atorva) 10 mg fixed-dose combination (FDC) tablet orally with food once daily for 52 weeks.	EZ 10 mg/Atorva 20 mg FDC n=18 Participants One EZ 10 mg/Atorva 20 mg fixed -dose combination (FDC) tablet orally with food once daily for 52 weeks.
Percentage of Participants Who Experience 1 or More Allergic Reaction or Rash AEs	6.8 Percentage of Participants	22.2 Percentage of Participants

PRIMARY outcome

Timeframe: up to 54 weeks

Population: All participants that received at least 1 dose of study drug and had available data for endpoint.

Hepatitis-related AEs included Cholestasis, Cytolytic Hepatitis, Hepatic Cyst, Hepatic Failure, Hepatic Lesion, Hepatic Necrosis, Hepatitis, Hepatitis Cholestatic, Hepatitis Fulminant, Hepatitis Infectious, Hepatocellular Injury, Hepatomegaly, Jaundice, Jaundice Cholestatic.

Outcome measures

Outcome measures
Measure	EZ 10 mg/Atorva 10 mg FDC n=117 Participants One ezetimibe (EZ) 10 mg/atorvastatin (Atorva) 10 mg fixed-dose combination (FDC) tablet orally with food once daily for 52 weeks.	EZ 10 mg/Atorva 20 mg FDC n=18 Participants One EZ 10 mg/Atorva 20 mg fixed -dose combination (FDC) tablet orally with food once daily for 52 weeks.
Percentage of Participants Who Experience 1 or More Hepatitis-related AEs	0.0 Percentage of Participants	5.6 Percentage of Participants

PRIMARY outcome

Timeframe: up to 52 weeks

Population: All participants that received at least 1 dose of study drug and had available data for endpoint.

Participants had ALT and AST levels assessed throughout the 52 week treatment period. Participants who had 2 consecutive assessments of ALT and/or AST that were 3 x ULN or greater were recorded. The ALT and AST ULNs were 40 U/L.

Outcome measures

Outcome measures
Measure	EZ 10 mg/Atorva 10 mg FDC n=117 Participants One ezetimibe (EZ) 10 mg/atorvastatin (Atorva) 10 mg fixed-dose combination (FDC) tablet orally with food once daily for 52 weeks.	EZ 10 mg/Atorva 20 mg FDC n=18 Participants One EZ 10 mg/Atorva 20 mg fixed -dose combination (FDC) tablet orally with food once daily for 52 weeks.
Percentage of Participants Who Experience Consecutive Elevations in Alanine Aminotransferase (ALT) and/or Aspartate Aminotransferase (AST) ≥3 Times Upper Normal Limit (ULN)	0.9 Percentage of Participants	0.0 Percentage of Participants

PRIMARY outcome

Timeframe: up to 52 weeks

Population: All participants that received at least 1 dose of study drug and had available data for endpoint.

Participants had ALT and AST levels assessed throughout the 52 week treatment period. Participants who had assessments of ALT or AST that were 5x ULN or greater were recorded. The ALT and AST ULNs were 40 U/L.

Outcome measures

Outcome measures
Measure	EZ 10 mg/Atorva 10 mg FDC n=117 Participants One ezetimibe (EZ) 10 mg/atorvastatin (Atorva) 10 mg fixed-dose combination (FDC) tablet orally with food once daily for 52 weeks.	EZ 10 mg/Atorva 20 mg FDC n=18 Participants One EZ 10 mg/Atorva 20 mg fixed -dose combination (FDC) tablet orally with food once daily for 52 weeks.
Percentage of Participants Who Experience Elevations in ALT or AST ≥5 Times ULN	0.0 Percentage of Participants	0.0 Percentage of Participants

PRIMARY outcome

Timeframe: up to 52 weeks

Population: All participants that received at least 1 dose of study drug and had available data for endpoint.

Participants had ALT and AST levels assessed throughout the 52 week treatment period. Participants who had assessments of ALT and/or AST that were 10x ULN or greater were recorded. The ALT and AST ULNs were 40 U/L.

Outcome measures

Outcome measures
Measure	EZ 10 mg/Atorva 10 mg FDC n=117 Participants One ezetimibe (EZ) 10 mg/atorvastatin (Atorva) 10 mg fixed-dose combination (FDC) tablet orally with food once daily for 52 weeks.	EZ 10 mg/Atorva 20 mg FDC n=18 Participants One EZ 10 mg/Atorva 20 mg fixed -dose combination (FDC) tablet orally with food once daily for 52 weeks.
Percentage of Participants Who Experience Elevations in ALT or AST ≥10 Times ULN	0.0 Percentage of Participants	0.0 Percentage of Participants

PRIMARY outcome

Timeframe: up to 52 weeks

Population: All participants that received at least 1 dose of study drug and had available data for endpoint.

Percentage of Participants with Potential Hy's Law Condition (defined as serum ALT or serum AST elevations \>3xULN, with serum alkaline phosphatase \<2xULN and total bilirubin (TBL) ≥2xULN) was summarized. The ALT and AST ULNs were 40 U/L. The ULN for alkaline phosphatase was 359 IU/L and the ULN for total bilirubin was 1.2 mg/dL.

Outcome measures

Outcome measures
Measure	EZ 10 mg/Atorva 10 mg FDC n=117 Participants One ezetimibe (EZ) 10 mg/atorvastatin (Atorva) 10 mg fixed-dose combination (FDC) tablet orally with food once daily for 52 weeks.	EZ 10 mg/Atorva 20 mg FDC n=18 Participants One EZ 10 mg/Atorva 20 mg fixed -dose combination (FDC) tablet orally with food once daily for 52 weeks.
Percentage of Participants With Potential Hy's Law Condition	0.0 Percentage of Participants	0.0 Percentage of Participants

PRIMARY outcome

Timeframe: up to 52 weeks

Population: All participants that received at least 1 dose of study drug and had available data for endpoint.

Participants had creatine phosphokinase (CK) levels assessed throughout the 12 week treatment period. Participants who had any CK level that was ≥10 x ULN were recorded. The CK ULNs for males and females were 287 IU/L and 163 IU/L, respectively.

Outcome measures

Outcome measures
Measure	EZ 10 mg/Atorva 10 mg FDC n=117 Participants One ezetimibe (EZ) 10 mg/atorvastatin (Atorva) 10 mg fixed-dose combination (FDC) tablet orally with food once daily for 52 weeks.	EZ 10 mg/Atorva 20 mg FDC n=18 Participants One EZ 10 mg/Atorva 20 mg fixed -dose combination (FDC) tablet orally with food once daily for 52 weeks.
Percentage of Participants Who Experience Elevations in Creatine Kinase (CK) ≥10 Times ULN	0.0 Percentage of Participants	0.0 Percentage of Participants

PRIMARY outcome

Timeframe: up to 52 weeks

Population: All participants that received at least 1 dose of study drug and had available data for endpoint.

Participants had CK levels assessed throughout the 52 week treatment period. Participants who had any CK level that was ≥10 x ULN and had associated muscle symptoms present within +/- 7 days were recorded. The CK ULNs for males and females were 287 IU/L and 163 IU/L, respectively.

Outcome measures

Outcome measures
Measure	EZ 10 mg/Atorva 10 mg FDC n=117 Participants One ezetimibe (EZ) 10 mg/atorvastatin (Atorva) 10 mg fixed-dose combination (FDC) tablet orally with food once daily for 52 weeks.	EZ 10 mg/Atorva 20 mg FDC n=18 Participants One EZ 10 mg/Atorva 20 mg fixed -dose combination (FDC) tablet orally with food once daily for 52 weeks.
Percentage of Participants Who Experience Elevations in Creatine Kinase (CK) ≥10 Times ULN With Muscle Symptoms	0.0 Percentage of Participants	0.0 Percentage of Participants

PRIMARY outcome

Timeframe: up to 52 weeks

Population: All participants that received at least 1 dose of study drug and had available data for endpoint.

Participants had CK levels assessed throughout the 52 week treatment period. Participants who had any CK level that was ≥10 x ULN and had associated muscle symptoms present within +/- 7 days that were reported as at least possibly-related to study drug were recorded. The CK ULNs for males and females were 287 IU/L and 163 IU/L, respectively.

Outcome measures

Outcome measures
Measure	EZ 10 mg/Atorva 10 mg FDC n=117 Participants One ezetimibe (EZ) 10 mg/atorvastatin (Atorva) 10 mg fixed-dose combination (FDC) tablet orally with food once daily for 52 weeks.	EZ 10 mg/Atorva 20 mg FDC n=18 Participants One EZ 10 mg/Atorva 20 mg fixed -dose combination (FDC) tablet orally with food once daily for 52 weeks.
Percentage of Participants Who Experience Elevations in Creatine Kinase (CK) ≥10 Times ULN and Drug-Related Muscle Symptoms	0.0 Percentage of Participants	0.0 Percentage of Participants

Adverse Events

EZ10/AT10

Serious events: 7 serious events

Other events: 77 other events

Deaths: 0 deaths

EZ10/AT20

Serious events: 2 serious events

Other events: 16 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	EZ10/AT10 n=117 participants at risk One ezetimibe (EZ) 10 mg/atorvastatin (Atorva) 10 mg fixed-dose combination (FDC) tablet orally with food once daily for 52 weeks.	EZ10/AT20 n=18 participants at risk One EZ 10 mg/Atorva 20 mg fixed -dose combination (FDC) tablet orally with food once daily for 52 weeks.
Cardiac disorders Angina pectoris	0.85% 1/117 • Number of events 1 • Up to 54 weeks Population included all participants that received at least 1 dose of study drug.	0.00% 0/18 • Up to 54 weeks Population included all participants that received at least 1 dose of study drug.
Cardiac disorders Myocardial ischaemia	0.85% 1/117 • Number of events 1 • Up to 54 weeks Population included all participants that received at least 1 dose of study drug.	0.00% 0/18 • Up to 54 weeks Population included all participants that received at least 1 dose of study drug.
Gastrointestinal disorders Colitis ischaemic	0.85% 1/117 • Number of events 1 • Up to 54 weeks Population included all participants that received at least 1 dose of study drug.	0.00% 0/18 • Up to 54 weeks Population included all participants that received at least 1 dose of study drug.
Gastrointestinal disorders Inguinal hernia	0.85% 1/117 • Number of events 1 • Up to 54 weeks Population included all participants that received at least 1 dose of study drug.	0.00% 0/18 • Up to 54 weeks Population included all participants that received at least 1 dose of study drug.
Injury, poisoning and procedural complications Contusion	0.85% 1/117 • Number of events 1 • Up to 54 weeks Population included all participants that received at least 1 dose of study drug.	0.00% 0/18 • Up to 54 weeks Population included all participants that received at least 1 dose of study drug.
Injury, poisoning and procedural complications Extradural haematoma	0.00% 0/117 • Up to 54 weeks Population included all participants that received at least 1 dose of study drug.	5.6% 1/18 • Number of events 1 • Up to 54 weeks Population included all participants that received at least 1 dose of study drug.
Injury, poisoning and procedural complications Subdural haematoma	0.00% 0/117 • Up to 54 weeks Population included all participants that received at least 1 dose of study drug.	5.6% 1/18 • Number of events 1 • Up to 54 weeks Population included all participants that received at least 1 dose of study drug.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lung neoplasm malignant	0.00% 0/117 • Up to 54 weeks Population included all participants that received at least 1 dose of study drug.	5.6% 1/18 • Number of events 1 • Up to 54 weeks Population included all participants that received at least 1 dose of study drug.
Nervous system disorders Cerebral infarction	0.85% 1/117 • Number of events 1 • Up to 54 weeks Population included all participants that received at least 1 dose of study drug.	0.00% 0/18 • Up to 54 weeks Population included all participants that received at least 1 dose of study drug.
Nervous system disorders Progressive supranuclear palsy	0.85% 1/117 • Number of events 1 • Up to 54 weeks Population included all participants that received at least 1 dose of study drug.	0.00% 0/18 • Up to 54 weeks Population included all participants that received at least 1 dose of study drug.
Renal and urinary disorders Glomerulonephritis membranous	0.85% 1/117 • Number of events 1 • Up to 54 weeks Population included all participants that received at least 1 dose of study drug.	0.00% 0/18 • Up to 54 weeks Population included all participants that received at least 1 dose of study drug.
Renal and urinary disorders Ureterolithiasis	0.85% 1/117 • Number of events 1 • Up to 54 weeks Population included all participants that received at least 1 dose of study drug.	0.00% 0/18 • Up to 54 weeks Population included all participants that received at least 1 dose of study drug.

Other adverse events

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

Measure	EZ10/AT10 n=117 participants at risk One ezetimibe (EZ) 10 mg/atorvastatin (Atorva) 10 mg fixed-dose combination (FDC) tablet orally with food once daily for 52 weeks.	EZ10/AT20 n=18 participants at risk One EZ 10 mg/Atorva 20 mg fixed -dose combination (FDC) tablet orally with food once daily for 52 weeks.
Ear and labyrinth disorders Sudden hearing loss	0.00% 0/117 • Up to 54 weeks Population included all participants that received at least 1 dose of study drug.	5.6% 1/18 • Number of events 1 • Up to 54 weeks Population included all participants that received at least 1 dose of study drug.
Eye disorders Scintillating scotoma	0.00% 0/117 • Up to 54 weeks Population included all participants that received at least 1 dose of study drug.	5.6% 1/18 • Number of events 1 • Up to 54 weeks Population included all participants that received at least 1 dose of study drug.
Gastrointestinal disorders Diarrhoea	1.7% 2/117 • Number of events 2 • Up to 54 weeks Population included all participants that received at least 1 dose of study drug.	5.6% 1/18 • Number of events 1 • Up to 54 weeks Population included all participants that received at least 1 dose of study drug.
Gastrointestinal disorders Gastritis	5.1% 6/117 • Number of events 6 • Up to 54 weeks Population included all participants that received at least 1 dose of study drug.	0.00% 0/18 • Up to 54 weeks Population included all participants that received at least 1 dose of study drug.
Gastrointestinal disorders Oral hyperaesthesia	0.00% 0/117 • Up to 54 weeks Population included all participants that received at least 1 dose of study drug.	5.6% 1/18 • Number of events 1 • Up to 54 weeks Population included all participants that received at least 1 dose of study drug.
Gastrointestinal disorders Periodontal disease	1.7% 2/117 • Number of events 2 • Up to 54 weeks Population included all participants that received at least 1 dose of study drug.	5.6% 1/18 • Number of events 1 • Up to 54 weeks Population included all participants that received at least 1 dose of study drug.
General disorders Chest discomfort	0.00% 0/117 • Up to 54 weeks Population included all participants that received at least 1 dose of study drug.	5.6% 1/18 • Number of events 1 • Up to 54 weeks Population included all participants that received at least 1 dose of study drug.
General disorders Fatigue	0.00% 0/117 • Up to 54 weeks Population included all participants that received at least 1 dose of study drug.	5.6% 1/18 • Number of events 1 • Up to 54 weeks Population included all participants that received at least 1 dose of study drug.
General disorders Malaise	0.00% 0/117 • Up to 54 weeks Population included all participants that received at least 1 dose of study drug.	5.6% 1/18 • Number of events 1 • Up to 54 weeks Population included all participants that received at least 1 dose of study drug.
General disorders Pyrexia	0.85% 1/117 • Number of events 1 • Up to 54 weeks Population included all participants that received at least 1 dose of study drug.	5.6% 1/18 • Number of events 1 • Up to 54 weeks Population included all participants that received at least 1 dose of study drug.
Hepatobiliary disorders Hepatic cyst	0.00% 0/117 • Up to 54 weeks Population included all participants that received at least 1 dose of study drug.	5.6% 1/18 • Number of events 1 • Up to 54 weeks Population included all participants that received at least 1 dose of study drug.
Infections and infestations Bronchitis	0.85% 1/117 • Number of events 1 • Up to 54 weeks Population included all participants that received at least 1 dose of study drug.	5.6% 1/18 • Number of events 1 • Up to 54 weeks Population included all participants that received at least 1 dose of study drug.
Infections and infestations Gastroenteritis	2.6% 3/117 • Number of events 3 • Up to 54 weeks Population included all participants that received at least 1 dose of study drug.	5.6% 1/18 • Number of events 1 • Up to 54 weeks Population included all participants that received at least 1 dose of study drug.
Infections and infestations Nasopharyngitis	42.7% 50/117 • Number of events 75 • Up to 54 weeks Population included all participants that received at least 1 dose of study drug.	38.9% 7/18 • Number of events 13 • Up to 54 weeks Population included all participants that received at least 1 dose of study drug.
Infections and infestations Paronychia	0.00% 0/117 • Up to 54 weeks Population included all participants that received at least 1 dose of study drug.	5.6% 1/18 • Number of events 1 • Up to 54 weeks Population included all participants that received at least 1 dose of study drug.
Infections and infestations Periodontitis	0.00% 0/117 • Up to 54 weeks Population included all participants that received at least 1 dose of study drug.	5.6% 1/18 • Number of events 1 • Up to 54 weeks Population included all participants that received at least 1 dose of study drug.
Infections and infestations Pharyngitis	5.1% 6/117 • Number of events 6 • Up to 54 weeks Population included all participants that received at least 1 dose of study drug.	0.00% 0/18 • Up to 54 weeks Population included all participants that received at least 1 dose of study drug.
Infections and infestations Subcutaneous abscess	0.00% 0/117 • Up to 54 weeks Population included all participants that received at least 1 dose of study drug.	5.6% 1/18 • Number of events 1 • Up to 54 weeks Population included all participants that received at least 1 dose of study drug.
Injury, poisoning and procedural complications Ligament injury	0.00% 0/117 • Up to 54 weeks Population included all participants that received at least 1 dose of study drug.	5.6% 1/18 • Number of events 1 • Up to 54 weeks Population included all participants that received at least 1 dose of study drug.
Injury, poisoning and procedural complications Muscle strain	0.00% 0/117 • Up to 54 weeks Population included all participants that received at least 1 dose of study drug.	5.6% 1/18 • Number of events 2 • Up to 54 weeks Population included all participants that received at least 1 dose of study drug.
Investigations Alanine aminotransferase increased	2.6% 3/117 • Number of events 3 • Up to 54 weeks Population included all participants that received at least 1 dose of study drug.	5.6% 1/18 • Number of events 1 • Up to 54 weeks Population included all participants that received at least 1 dose of study drug.
Investigations Aspartate aminotransferase increased	0.00% 0/117 • Up to 54 weeks Population included all participants that received at least 1 dose of study drug.	5.6% 1/18 • Number of events 1 • Up to 54 weeks Population included all participants that received at least 1 dose of study drug.
Investigations Blood creatine phosphokinase increased	0.85% 1/117 • Number of events 1 • Up to 54 weeks Population included all participants that received at least 1 dose of study drug.	5.6% 1/18 • Number of events 1 • Up to 54 weeks Population included all participants that received at least 1 dose of study drug.
Investigations Electrocardiogram ST-T segment depression	0.00% 0/117 • Up to 54 weeks Population included all participants that received at least 1 dose of study drug.	5.6% 1/18 • Number of events 1 • Up to 54 weeks Population included all participants that received at least 1 dose of study drug.
Metabolism and nutrition disorders Type 2 diabetes mellitus	9.4% 11/117 • Number of events 11 • Up to 54 weeks Population included all participants that received at least 1 dose of study drug.	11.1% 2/18 • Number of events 2 • Up to 54 weeks Population included all participants that received at least 1 dose of study drug.
Musculoskeletal and connective tissue disorders Arthralgia	1.7% 2/117 • Number of events 2 • Up to 54 weeks Population included all participants that received at least 1 dose of study drug.	5.6% 1/18 • Number of events 1 • Up to 54 weeks Population included all participants that received at least 1 dose of study drug.
Musculoskeletal and connective tissue disorders Back pain	7.7% 9/117 • Number of events 9 • Up to 54 weeks Population included all participants that received at least 1 dose of study drug.	5.6% 1/18 • Number of events 1 • Up to 54 weeks Population included all participants that received at least 1 dose of study drug.
Musculoskeletal and connective tissue disorders Myalgia	1.7% 2/117 • Number of events 2 • Up to 54 weeks Population included all participants that received at least 1 dose of study drug.	5.6% 1/18 • Number of events 1 • Up to 54 weeks Population included all participants that received at least 1 dose of study drug.
Musculoskeletal and connective tissue disorders Osteoarthritis	3.4% 4/117 • Number of events 4 • Up to 54 weeks Population included all participants that received at least 1 dose of study drug.	5.6% 1/18 • Number of events 1 • Up to 54 weeks Population included all participants that received at least 1 dose of study drug.
Musculoskeletal and connective tissue disorders Pain in extremity	1.7% 2/117 • Number of events 2 • Up to 54 weeks Population included all participants that received at least 1 dose of study drug.	5.6% 1/18 • Number of events 1 • Up to 54 weeks Population included all participants that received at least 1 dose of study drug.
Nervous system disorders Headache	5.1% 6/117 • Number of events 10 • Up to 54 weeks Population included all participants that received at least 1 dose of study drug.	5.6% 1/18 • Number of events 1 • Up to 54 weeks Population included all participants that received at least 1 dose of study drug.
Nervous system disorders Hypoaesthesia	0.00% 0/117 • Up to 54 weeks Population included all participants that received at least 1 dose of study drug.	11.1% 2/18 • Number of events 2 • Up to 54 weeks Population included all participants that received at least 1 dose of study drug.
Nervous system disorders Sciatica	2.6% 3/117 • Number of events 3 • Up to 54 weeks Population included all participants that received at least 1 dose of study drug.	5.6% 1/18 • Number of events 1 • Up to 54 weeks Population included all participants that received at least 1 dose of study drug.
Renal and urinary disorders Cystitis noninfective	0.00% 0/117 • Up to 54 weeks Population included all participants that received at least 1 dose of study drug.	5.6% 1/18 • Number of events 1 • Up to 54 weeks Population included all participants that received at least 1 dose of study drug.
Renal and urinary disorders Nephrolithiasis	0.00% 0/117 • Up to 54 weeks Population included all participants that received at least 1 dose of study drug.	5.6% 1/18 • Number of events 1 • Up to 54 weeks Population included all participants that received at least 1 dose of study drug.
Renal and urinary disorders Renal cyst	0.00% 0/117 • Up to 54 weeks Population included all participants that received at least 1 dose of study drug.	5.6% 1/18 • Number of events 1 • Up to 54 weeks Population included all participants that received at least 1 dose of study drug.
Respiratory, thoracic and mediastinal disorders Cough	0.00% 0/117 • Up to 54 weeks Population included all participants that received at least 1 dose of study drug.	5.6% 1/18 • Number of events 1 • Up to 54 weeks Population included all participants that received at least 1 dose of study drug.
Respiratory, thoracic and mediastinal disorders Nasal congestion	0.00% 0/117 • Up to 54 weeks Population included all participants that received at least 1 dose of study drug.	5.6% 1/18 • Number of events 1 • Up to 54 weeks Population included all participants that received at least 1 dose of study drug.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	0.00% 0/117 • Up to 54 weeks Population included all participants that received at least 1 dose of study drug.	5.6% 1/18 • Number of events 1 • Up to 54 weeks Population included all participants that received at least 1 dose of study drug.
Respiratory, thoracic and mediastinal disorders Upper respiratory tract inflammation	0.85% 1/117 • Number of events 1 • Up to 54 weeks Population included all participants that received at least 1 dose of study drug.	5.6% 1/18 • Number of events 1 • Up to 54 weeks Population included all participants that received at least 1 dose of study drug.
Skin and subcutaneous tissue disorders Acne	0.00% 0/117 • Up to 54 weeks Population included all participants that received at least 1 dose of study drug.	5.6% 1/18 • Number of events 1 • Up to 54 weeks Population included all participants that received at least 1 dose of study drug.
Skin and subcutaneous tissue disorders Dermatitis	0.85% 1/117 • Number of events 1 • Up to 54 weeks Population included all participants that received at least 1 dose of study drug.	5.6% 1/18 • Number of events 1 • Up to 54 weeks Population included all participants that received at least 1 dose of study drug.
Skin and subcutaneous tissue disorders Dermatitis allergic	0.85% 1/117 • Number of events 1 • Up to 54 weeks Population included all participants that received at least 1 dose of study drug.	5.6% 1/18 • Number of events 1 • Up to 54 weeks Population included all participants that received at least 1 dose of study drug.
Skin and subcutaneous tissue disorders Eczema	1.7% 2/117 • Number of events 3 • Up to 54 weeks Population included all participants that received at least 1 dose of study drug.	5.6% 1/18 • Number of events 1 • Up to 54 weeks Population included all participants that received at least 1 dose of study drug.
Skin and subcutaneous tissue disorders Rash	0.00% 0/117 • Up to 54 weeks Population included all participants that received at least 1 dose of study drug.	5.6% 1/18 • Number of events 1 • Up to 54 weeks Population included all participants that received at least 1 dose of study drug.