Trial Outcomes & Findings for POS vs FLU for First Line Treatment of Coccidioidomycosis (Study P04558Am1)(COMPLETED) (NCT NCT00423267)

NCT ID: NCT00423267

Last Updated: 2017-04-11

Results Overview

Treatment-emergent adverse events are defined as new events that occur following subject entry into the study or events that worsen following study entry state. Treatment-related adverse events are defined as new events that occur following subject entry into the study or events that worsen following study entry state and are judged by the investigator to be possibly, probably or definitely related to study medication.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 16 participants
• Primary outcome timeframe: 12 months
• Results posted on: 2017-04-11

Participant Flow

Participant milestones

Measure	Posaconazole Eligible subjects will be stratified at Baseline by disease site (skeletal, lung, or soft tissue) and by immune status (immunocompromised or non-immunocompromised) and will then be randomly assigned to receive Posaconazole 400 mg orally (PO) (oral suspension 40 mg/mL) administered twice daily with meals or oral nutritional supplements for 12 months. One subject from period A declined to participate in the amended protocol and discontinued study treatment after 12 months of study drug administration.	Fluconazole Eligible subjects will be stratified at Baseline by disease site (skeletal, lung, or soft tissue) and by immune status (immunocompromised or non-immunocompromised) and will then be randomly assigned to receive Fluconazole 400 mg PO (given as two 200-mg oral encapsulated tablets) administered once daily for 12 months. Fluconazole treatment or placebo only occurred during Period A. Participants in this arm were given posaconazole in Period B.
Period A STARTED	9	7
Period A COMPLETED	7	6
Period A NOT COMPLETED	2	1
Period B STARTED	12	0
Period B COMPLETED	12	0
Period B NOT COMPLETED	0	0

Reasons for withdrawal

Measure	Posaconazole Eligible subjects will be stratified at Baseline by disease site (skeletal, lung, or soft tissue) and by immune status (immunocompromised or non-immunocompromised) and will then be randomly assigned to receive Posaconazole 400 mg orally (PO) (oral suspension 40 mg/mL) administered twice daily with meals or oral nutritional supplements for 12 months. One subject from period A declined to participate in the amended protocol and discontinued study treatment after 12 months of study drug administration.	Fluconazole Eligible subjects will be stratified at Baseline by disease site (skeletal, lung, or soft tissue) and by immune status (immunocompromised or non-immunocompromised) and will then be randomly assigned to receive Fluconazole 400 mg PO (given as two 200-mg oral encapsulated tablets) administered once daily for 12 months. Fluconazole treatment or placebo only occurred during Period A. Participants in this arm were given posaconazole in Period B.
Period A Withdrawal by Subject	0	1
Period A Non-compliance with protocol	1	0
Period A Administrative	1	0

Baseline Characteristics

POS vs FLU for First Line Treatment of Coccidioidomycosis (Study P04558Am1)(COMPLETED)

Baseline characteristics by cohort

Measure	Posaconazole n=9 Participants Eligible subjects will be stratified at Baseline by disease site (skeletal, lung, or soft tissue) and by immune status (immunocompromised or non-immunocompromised) and will then be randomly assigned to receive Posaconazole 400 mg orally (PO) (oral suspension 40 mg/mL) administered twice daily with meals or oral nutritional supplements for 12 months.	Fluconazole n=7 Participants Eligible subjects will be stratified at Baseline by disease site (skeletal, lung, or soft tissue) and by immune status (immunocompromised or non-immunocompromised) and will then be randomly assigned to receive Fluconazole 400 mg PO (given as two 200-mg oral encapsulated tablets) administered once daily for 12 months. Fluconazole treatment or placebo only occurred during Period A. Participants in this arm were given posaconazole in Period B.	Total n=16 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	7 Participants n=5 Participants	7 Participants n=7 Participants	14 Participants n=5 Participants
Age, Categorical >=65 years	2 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants
Sex: Female, Male Female	4 Participants n=5 Participants	2 Participants n=7 Participants	6 Participants n=5 Participants
Sex: Female, Male Male	5 Participants n=5 Participants	5 Participants n=7 Participants	10 Participants n=5 Participants

PRIMARY outcome

Timeframe: 12 months

Treatment-emergent adverse events are defined as new events that occur following subject entry into the study or events that worsen following study entry state.

Treatment-related adverse events are defined as new events that occur following subject entry into the study or events that worsen following study entry state and are judged by the investigator to be possibly, probably or definitely related to study medication.

Outcome measures

Measure	Posaconazole n=9 Participants Eligible subjects will be stratified at Baseline by disease site (skeletal, lung, or soft tissue) and by immune status (immunocompromised or non-immunocompromised) and will then be randomly assigned to receive Posaconazole 400 mg orally (PO) (oral suspension 40 mg/mL) administered twice daily with meals or oral nutritional supplements for 12 months.	Fluconazole n=7 Participants Eligible subjects will be stratified at Baseline by disease site (skeletal, lung, or soft tissue) and by immune status (immunocompromised or non-immunocompromised) and will then be randomly assigned to receive Fluconazole 400 mg PO (given as two 200-mg oral encapsulated tablets) administered once daily for 12 months. Fluconazole treatment or placebo only occurred during Period A. Participants in this arm were given posaconazole in Period B.
Number of Participants With Treatment-related Treatment-emergent Adverse Events (TRAEs) That Occurred With Posaconazole (POS) or Fluconazole (FLU) in Period A	5 Participants	3 Participants

PRIMARY outcome

Timeframe: 12 months

Treatment-emergent adverse events are defined as new events that occur following subject entry into the study or events that worsen following study entry state.

Treatment-related adverse events are defined as new events that occur following subject entry into the study or events that worsen following study entry state and are judged by the investigator to be possibly, probably or definitely related to study medication.

Outcome measures

Measure	Posaconazole n=12 Participants Eligible subjects will be stratified at Baseline by disease site (skeletal, lung, or soft tissue) and by immune status (immunocompromised or non-immunocompromised) and will then be randomly assigned to receive Posaconazole 400 mg orally (PO) (oral suspension 40 mg/mL) administered twice daily with meals or oral nutritional supplements for 12 months.	Fluconazole Eligible subjects will be stratified at Baseline by disease site (skeletal, lung, or soft tissue) and by immune status (immunocompromised or non-immunocompromised) and will then be randomly assigned to receive Fluconazole 400 mg PO (given as two 200-mg oral encapsulated tablets) administered once daily for 12 months. Fluconazole treatment or placebo only occurred during Period A. Participants in this arm were given posaconazole in Period B.
Number of Participants With Treatment-related Treatment-emergent Adverse Events (TRAEs) That Occurred With Posaconazole (POS) in Period B	3 Participants	—

SECONDARY outcome

Timeframe: 12 months

Treatment-emergent adverse events are defined as new events that occur following subject entry into the study or events that worsen following study entry state.

Outcome measures

Measure	Posaconazole n=9 Participants Eligible subjects will be stratified at Baseline by disease site (skeletal, lung, or soft tissue) and by immune status (immunocompromised or non-immunocompromised) and will then be randomly assigned to receive Posaconazole 400 mg orally (PO) (oral suspension 40 mg/mL) administered twice daily with meals or oral nutritional supplements for 12 months.	Fluconazole n=7 Participants Eligible subjects will be stratified at Baseline by disease site (skeletal, lung, or soft tissue) and by immune status (immunocompromised or non-immunocompromised) and will then be randomly assigned to receive Fluconazole 400 mg PO (given as two 200-mg oral encapsulated tablets) administered once daily for 12 months. Fluconazole treatment or placebo only occurred during Period A. Participants in this arm were given posaconazole in Period B.
Number of Participants With Treatment-emergent Adverse Events (TEAEs)That Occurred With POS or FLU in Period A	8 Participants	5 Participants

SECONDARY outcome

Timeframe: 12 months

Treatment-emergent adverse events are defined as new events that occur following subject entry into the study or events that worsen following study entry state.

Outcome measures

Measure	Posaconazole n=12 Participants Eligible subjects will be stratified at Baseline by disease site (skeletal, lung, or soft tissue) and by immune status (immunocompromised or non-immunocompromised) and will then be randomly assigned to receive Posaconazole 400 mg orally (PO) (oral suspension 40 mg/mL) administered twice daily with meals or oral nutritional supplements for 12 months.	Fluconazole Eligible subjects will be stratified at Baseline by disease site (skeletal, lung, or soft tissue) and by immune status (immunocompromised or non-immunocompromised) and will then be randomly assigned to receive Fluconazole 400 mg PO (given as two 200-mg oral encapsulated tablets) administered once daily for 12 months. Fluconazole treatment or placebo only occurred during Period A. Participants in this arm were given posaconazole in Period B.
Number of Participants With Treatment-emergent Adverse Events (TEAEs) That Occurred With POS in Period B	8 Participants	—

SECONDARY outcome

Timeframe: 12 months

Severity grading was based on Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0. This is a descriptive terminology which can be utilized for Adverse Event (AE) reporting. A grading (severity) scale is provided for each AE term. CTCAE displays Grades 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline: Grade 1 Mild AE; Grade 2 Moderate AE; Grade 3 Severe AE; Grade 4 Life-threatening or disabling AE; Grade 5 Death related to AE.

Outcome measures

Measure	Posaconazole n=9 Participants Eligible subjects will be stratified at Baseline by disease site (skeletal, lung, or soft tissue) and by immune status (immunocompromised or non-immunocompromised) and will then be randomly assigned to receive Posaconazole 400 mg orally (PO) (oral suspension 40 mg/mL) administered twice daily with meals or oral nutritional supplements for 12 months.	Fluconazole n=7 Participants Eligible subjects will be stratified at Baseline by disease site (skeletal, lung, or soft tissue) and by immune status (immunocompromised or non-immunocompromised) and will then be randomly assigned to receive Fluconazole 400 mg PO (given as two 200-mg oral encapsulated tablets) administered once daily for 12 months. Fluconazole treatment or placebo only occurred during Period A. Participants in this arm were given posaconazole in Period B.
Number of Participants With Laboratory Test Abnormalities (at Least a 1 Grade Shift From Baseline) That Occurred With POS or FLU in Period A Renal function tests	0 Participants	1 Participants
Number of Participants With Laboratory Test Abnormalities (at Least a 1 Grade Shift From Baseline) That Occurred With POS or FLU in Period A Hematology	4 Participants	1 Participants
Number of Participants With Laboratory Test Abnormalities (at Least a 1 Grade Shift From Baseline) That Occurred With POS or FLU in Period A Liver function tests	4 Participants	3 Participants
Number of Participants With Laboratory Test Abnormalities (at Least a 1 Grade Shift From Baseline) That Occurred With POS or FLU in Period A Electrolytes	0 Participants	2 Participants

SECONDARY outcome

Timeframe: 12 months

Severity grading was based on Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0. This is a descriptive terminology which can be utilized for Adverse Event (AE) reporting. A grading (severity) scale is provided for each AE term. CTCAE displays Grades 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline: Grade 1 Mild AE; Grade 2 Moderate AE; Grade 3 Severe AE; Grade 4 Life-threatening or disabling AE; Grade 5 Death related to AE.

Outcome measures

Measure	Posaconazole n=12 Participants Eligible subjects will be stratified at Baseline by disease site (skeletal, lung, or soft tissue) and by immune status (immunocompromised or non-immunocompromised) and will then be randomly assigned to receive Posaconazole 400 mg orally (PO) (oral suspension 40 mg/mL) administered twice daily with meals or oral nutritional supplements for 12 months.	Fluconazole Eligible subjects will be stratified at Baseline by disease site (skeletal, lung, or soft tissue) and by immune status (immunocompromised or non-immunocompromised) and will then be randomly assigned to receive Fluconazole 400 mg PO (given as two 200-mg oral encapsulated tablets) administered once daily for 12 months. Fluconazole treatment or placebo only occurred during Period A. Participants in this arm were given posaconazole in Period B.
Number of Participants With Laboratory Abnormalities (at Least a 1 Grade Shift From Baseline) That Occurred With POS in Period B Hematology	2 Participants	—
Number of Participants With Laboratory Abnormalities (at Least a 1 Grade Shift From Baseline) That Occurred With POS in Period B Liver function tests	11 Participants	—
Number of Participants With Laboratory Abnormalities (at Least a 1 Grade Shift From Baseline) That Occurred With POS in Period B Renal function tests	1 Participants	—
Number of Participants With Laboratory Abnormalities (at Least a 1 Grade Shift From Baseline) That Occurred With POS in Period B Electrolytes	0 Participants	—

SECONDARY outcome

Timeframe: 12 months

Outcome measures

Measure	Posaconazole n=9 Participants Eligible subjects will be stratified at Baseline by disease site (skeletal, lung, or soft tissue) and by immune status (immunocompromised or non-immunocompromised) and will then be randomly assigned to receive Posaconazole 400 mg orally (PO) (oral suspension 40 mg/mL) administered twice daily with meals or oral nutritional supplements for 12 months.	Fluconazole n=7 Participants Eligible subjects will be stratified at Baseline by disease site (skeletal, lung, or soft tissue) and by immune status (immunocompromised or non-immunocompromised) and will then be randomly assigned to receive Fluconazole 400 mg PO (given as two 200-mg oral encapsulated tablets) administered once daily for 12 months. Fluconazole treatment or placebo only occurred during Period A. Participants in this arm were given posaconazole in Period B.
Number of Participant Discontinuations Due to Adverse Events and/or Laboratory Evaluations of Safety in Period A	0 Participants	0 Participants

SECONDARY outcome

Timeframe: 12 months

Outcome measures

Measure	Posaconazole n=12 Participants Eligible subjects will be stratified at Baseline by disease site (skeletal, lung, or soft tissue) and by immune status (immunocompromised or non-immunocompromised) and will then be randomly assigned to receive Posaconazole 400 mg orally (PO) (oral suspension 40 mg/mL) administered twice daily with meals or oral nutritional supplements for 12 months.	Fluconazole Eligible subjects will be stratified at Baseline by disease site (skeletal, lung, or soft tissue) and by immune status (immunocompromised or non-immunocompromised) and will then be randomly assigned to receive Fluconazole 400 mg PO (given as two 200-mg oral encapsulated tablets) administered once daily for 12 months. Fluconazole treatment or placebo only occurred during Period A. Participants in this arm were given posaconazole in Period B.
Number of Participant Discontinuations Due to Adverse Events and/or Laboratory Evaluations of Safety in Period B	0 Participants	—

Adverse Events

Posaconazole Period A

Serious events: 0 serious events

Other events: 8 other events

Deaths: 0 deaths

Fluconazole Period A

Serious events: 0 serious events

Other events: 5 other events

Deaths: 0 deaths

Posaconazole Period B

Serious events: 1 serious events

Other events: 8 other events

Deaths: 0 deaths

Serious adverse events

Measure	Posaconazole Period A n=9 participants at risk	Fluconazole Period A n=7 participants at risk	Posaconazole Period B n=12 participants at risk
Injury, poisoning and procedural complications HIP FRACTURE	0.00% 0/9	0.00% 0/7	8.3% 1/12 • Number of events 1

Other adverse events

Measure	Posaconazole Period A n=9 participants at risk	Fluconazole Period A n=7 participants at risk	Posaconazole Period B n=12 participants at risk
Blood and lymphatic system disorders ANAEMIA	11.1% 1/9 • Number of events 1	0.00% 0/7	0.00% 0/12
Cardiac disorders BRADYCARDIA	11.1% 1/9 • Number of events 1	0.00% 0/7	0.00% 0/12
Cardiac disorders PALPITATIONS	11.1% 1/9 • Number of events 1	14.3% 1/7 • Number of events 1	0.00% 0/12
Ear and labyrinth disorders DEAFNESS	0.00% 0/9	0.00% 0/7	8.3% 1/12 • Number of events 1
Ear and labyrinth disorders VERTIGO	11.1% 1/9 • Number of events 1	0.00% 0/7	0.00% 0/12
Endocrine disorders HYPOTHYROIDISM	0.00% 0/9	14.3% 1/7 • Number of events 1	0.00% 0/12
Eye disorders DRY EYE	0.00% 0/9	14.3% 1/7 • Number of events 1	0.00% 0/12
Gastrointestinal disorders ABDOMINAL DISCOMFORT	0.00% 0/9	0.00% 0/7	8.3% 1/12 • Number of events 1
Gastrointestinal disorders CONSTIPATION	11.1% 1/9 • Number of events 1	14.3% 1/7 • Number of events 1	0.00% 0/12
Gastrointestinal disorders DIARRHOEA	22.2% 2/9 • Number of events 7	14.3% 1/7 • Number of events 1	0.00% 0/12
Gastrointestinal disorders DYSPEPSIA	0.00% 0/9	14.3% 1/7 • Number of events 1	0.00% 0/12
Gastrointestinal disorders GASTROOESOPHAGEAL REFLUX DISEASE	11.1% 1/9 • Number of events 1	0.00% 0/7	0.00% 0/12
Gastrointestinal disorders LIP DRY	0.00% 0/9	14.3% 1/7 • Number of events 1	0.00% 0/12
Gastrointestinal disorders VOMITING	11.1% 1/9 • Number of events 1	0.00% 0/7	0.00% 0/12
General disorders CHEST DISCOMFORT	11.1% 1/9 • Number of events 1	0.00% 0/7	0.00% 0/12
General disorders FATIGUE	11.1% 1/9 • Number of events 1	0.00% 0/7	0.00% 0/12
General disorders INFLUENZA LIKE ILLNESS	0.00% 0/9	14.3% 1/7 • Number of events 2	0.00% 0/12
General disorders OEDEMA PERIPHERAL	11.1% 1/9 • Number of events 1	0.00% 0/7	0.00% 0/12
General disorders SWELLING	11.1% 1/9 • Number of events 1	0.00% 0/7	0.00% 0/12
Hepatobiliary disorders CHOLELITHIASIS	11.1% 1/9 • Number of events 1	0.00% 0/7	8.3% 1/12 • Number of events 1
Infections and infestations BRONCHITIS VIRAL	11.1% 1/9 • Number of events 1	0.00% 0/7	0.00% 0/12
Infections and infestations BRONCHOPNEUMONIA	0.00% 0/9	0.00% 0/7	8.3% 1/12 • Number of events 1
Infections and infestations EAR INFECTION	0.00% 0/9	0.00% 0/7	8.3% 1/12 • Number of events 1
Infections and infestations HERPES ZOSTER	11.1% 1/9 • Number of events 1	0.00% 0/7	0.00% 0/12
Infections and infestations INCISION SITE INFECTION	0.00% 0/9	14.3% 1/7 • Number of events 1	0.00% 0/12
Infections and infestations NASOPHARYNGITIS	0.00% 0/9	14.3% 1/7 • Number of events 1	0.00% 0/12
Infections and infestations ORAL HERPES	11.1% 1/9 • Number of events 1	0.00% 0/7	0.00% 0/12
Infections and infestations PAROTITIS	11.1% 1/9 • Number of events 1	0.00% 0/7	0.00% 0/12
Infections and infestations PHARYNGITIS	0.00% 0/9	14.3% 1/7 • Number of events 1	0.00% 0/12
Infections and infestations RESPIRATORY TRACT INFECTION	11.1% 1/9 • Number of events 1	0.00% 0/7	0.00% 0/12
Infections and infestations SINUSITIS	0.00% 0/9	14.3% 1/7 • Number of events 1	0.00% 0/12
Infections and infestations UPPER RESPIRATORY TRACT INFECTION	0.00% 0/9	0.00% 0/7	8.3% 1/12 • Number of events 1
Infections and infestations URINARY TRACT INFECTION	0.00% 0/9	0.00% 0/7	8.3% 1/12 • Number of events 1
Injury, poisoning and procedural complications CONTUSION	11.1% 1/9 • Number of events 1	0.00% 0/7	0.00% 0/12
Injury, poisoning and procedural complications EXCORIATION	11.1% 1/9 • Number of events 1	0.00% 0/7	0.00% 0/12
Injury, poisoning and procedural complications FALL	0.00% 0/9	0.00% 0/7	8.3% 1/12 • Number of events 1
Injury, poisoning and procedural complications VENOMOUS STING	0.00% 0/9	14.3% 1/7 • Number of events 1	0.00% 0/12
Investigations BLOOD CREATININE INCREASED	0.00% 0/9	0.00% 0/7	8.3% 1/12 • Number of events 1
Investigations HEPATIC ENZYME INCREASED	0.00% 0/9	0.00% 0/7	8.3% 1/12 • Number of events 1
Investigations PLATELET COUNT INCREASED	0.00% 0/9	0.00% 0/7	8.3% 1/12 • Number of events 1
Metabolism and nutrition disorders HYPERTRIGLYCERIDAEMIA	0.00% 0/9	14.3% 1/7 • Number of events 1	0.00% 0/12
Musculoskeletal and connective tissue disorders ARTHRALGIA	33.3% 3/9 • Number of events 3	0.00% 0/7	0.00% 0/12
Musculoskeletal and connective tissue disorders BACK PAIN	11.1% 1/9 • Number of events 1	0.00% 0/7	0.00% 0/12
Musculoskeletal and connective tissue disorders MUSCLE FATIGUE	0.00% 0/9	14.3% 1/7 • Number of events 1	0.00% 0/12
Musculoskeletal and connective tissue disorders MUSCULAR WEAKNESS	0.00% 0/9	14.3% 1/7 • Number of events 1	0.00% 0/12
Musculoskeletal and connective tissue disorders MUSCULOSKELETAL STIFFNESS	11.1% 1/9 • Number of events 1	0.00% 0/7	0.00% 0/12
Musculoskeletal and connective tissue disorders MYALGIA	11.1% 1/9 • Number of events 1	0.00% 0/7	0.00% 0/12
Musculoskeletal and connective tissue disorders NECK PAIN	11.1% 1/9 • Number of events 1	0.00% 0/7	0.00% 0/12
Musculoskeletal and connective tissue disorders PAIN IN EXTREMITY	22.2% 2/9 • Number of events 2	0.00% 0/7	0.00% 0/12
Nervous system disorders DIZZINESS	0.00% 0/9	0.00% 0/7	8.3% 1/12 • Number of events 1
Nervous system disorders HEADACHE	0.00% 0/9	28.6% 2/7 • Number of events 2	0.00% 0/12
Nervous system disorders POST HERPETIC NEURALGIA	11.1% 1/9 • Number of events 1	0.00% 0/7	0.00% 0/12
Nervous system disorders SOMNOLENCE	11.1% 1/9 • Number of events 1	14.3% 1/7 • Number of events 1	0.00% 0/12
Psychiatric disorders ANXIETY	11.1% 1/9 • Number of events 1	0.00% 0/7	0.00% 0/12
Psychiatric disorders INSOMNIA	0.00% 0/9	28.6% 2/7 • Number of events 2	0.00% 0/12
Psychiatric disorders PANIC ATTACK	11.1% 1/9 • Number of events 2	0.00% 0/7	0.00% 0/12
Renal and urinary disorders DYSURIA	0.00% 0/9	14.3% 1/7 • Number of events 1	8.3% 1/12 • Number of events 1
Renal and urinary disorders URETERIC OBSTRUCTION	0.00% 0/9	14.3% 1/7 • Number of events 1	0.00% 0/12
Respiratory, thoracic and mediastinal disorders COUGH	0.00% 0/9	0.00% 0/7	8.3% 1/12 • Number of events 1
Respiratory, thoracic and mediastinal disorders DYSPNOEA	11.1% 1/9 • Number of events 1	0.00% 0/7	0.00% 0/12
Respiratory, thoracic and mediastinal disorders NASAL CONGESTION	0.00% 0/9	0.00% 0/7	8.3% 1/12 • Number of events 1
Respiratory, thoracic and mediastinal disorders NASAL DRYNESS	0.00% 0/9	14.3% 1/7 • Number of events 1	0.00% 0/12
Respiratory, thoracic and mediastinal disorders OROPHARYNGEAL PAIN	0.00% 0/9	14.3% 1/7 • Number of events 1	0.00% 0/12
Skin and subcutaneous tissue disorders DRY SKIN	0.00% 0/9	28.6% 2/7 • Number of events 2	0.00% 0/12
Skin and subcutaneous tissue disorders ERYTHEMA	11.1% 1/9 • Number of events 1	14.3% 1/7 • Number of events 1	8.3% 1/12 • Number of events 1
Skin and subcutaneous tissue disorders INGROWING NAIL	0.00% 0/9	0.00% 0/7	8.3% 1/12 • Number of events 1
Skin and subcutaneous tissue disorders PRURITUS	11.1% 1/9 • Number of events 1	14.3% 1/7 • Number of events 1	0.00% 0/12
Skin and subcutaneous tissue disorders RASH	22.2% 2/9 • Number of events 2	0.00% 0/7	8.3% 1/12 • Number of events 1
Skin and subcutaneous tissue disorders SWELLING FACE	22.2% 2/9 • Number of events 2	0.00% 0/7	0.00% 0/12
Vascular disorders BLEEDING VARICOSE VEIN	0.00% 0/9	0.00% 0/7	8.3% 1/12 • Number of events 1
Vascular disorders HYPERTENSION	0.00% 0/9	0.00% 0/7	8.3% 1/12 • Number of events 1
Vascular disorders THROMBOPHLEBITIS	0.00% 0/9	0.00% 0/7	8.3% 1/12 • Number of events 1
Vascular disorders VARICOSE VEIN	0.00% 0/9	0.00% 0/7	8.3% 1/12 • Number of events 1

Additional Information

Senior Vice President, Global Clinical Development

Merck Sharp & Dohme Corp.

Email: ClinicalTrialsDisclosure@merck.com

Results disclosure agreements

• Principal investigator is a sponsor employee The investigator agrees not to publish or present any interim results of the study without the Sponsor's prior written consent. The investigator further agrees to provide review copies to the Sponsor 45 days prior to submission for publication or presentation. The sponsor has the right to review and comment. If the parties disagree concerning the appropriateness of the data analysis and presentation, and/or confidentiality, investigator agrees to meet with the sponsor to discuss and resolve.
• Publication restrictions are in place

Restriction type: OTHER