Trial Outcomes & Findings for Multiple Dose Study Of PF-05231023 In Obese Adult Subjects (NCT NCT01923389)

NCT ID: NCT01923389

Last Updated: 2014-09-17

Results Overview

An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. AEs were also reported for the 7-day pre-randomization period.

Recruitment status

TERMINATED

Study phase

PHASE1

Target enrollment

4 participants

Primary outcome timeframe

Day -7 through the last follow-up (Day 68)

Results posted on

2014-09-17

Participant Flow

Participant milestones

Participant milestones
Measure	Placebo Placebo (normal saline) was administered as a 20-milliliters (mL) intravenous (IV) infusion twice weekly on Days 1, 4, 8, 11, 15, 18, 22 and 25.	PF-05231023 100 mg PF-05231023 100 mg was administered as a 20-mL IV infusion twice weekly on Days 1, 4, 8, 11, 15, 18, 22 and 25.
Overall Study STARTED	2	2
Overall Study COMPLETED	1	2
Overall Study NOT COMPLETED	1	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo Placebo (normal saline) was administered as a 20-milliliters (mL) intravenous (IV) infusion twice weekly on Days 1, 4, 8, 11, 15, 18, 22 and 25.	PF-05231023 100 mg PF-05231023 100 mg was administered as a 20-mL IV infusion twice weekly on Days 1, 4, 8, 11, 15, 18, 22 and 25.
Overall Study Protocol Violation	1	0

Baseline Characteristics

Multiple Dose Study Of PF-05231023 In Obese Adult Subjects

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=2 Participants Placebo (normal saline) was administered as a 20-mL IV infusion twice weekly on Days 1, 4, 8, 11, 15, 18, 22 and 25.	PF-05231023 100 mg n=2 Participants PF-05231023 100 mg was administered as a 20-mL IV infusion twice weekly on Days 1, 4, 8, 11, 15, 18, 22 and 25.	Total n=4 Participants Total of all reporting groups
Age, Continuous	39.0 years STANDARD_DEVIATION 4.2 • n=99 Participants	34.0 years STANDARD_DEVIATION 5.7 • n=107 Participants	36.5 years STANDARD_DEVIATION 5.0 • n=206 Participants
Sex: Female, Male Female	1 Participants n=99 Participants	0 Participants n=107 Participants	1 Participants n=206 Participants
Sex: Female, Male Male	1 Participants n=99 Participants	2 Participants n=107 Participants	3 Participants n=206 Participants

PRIMARY outcome

Timeframe: Day -7 through the last follow-up (Day 68)

Population: All participants who received at least 1 dose of study medication (PF-05231023 or placebo).

Outcome measures

Outcome measures
Measure	Placebo n=2 Participants Placebo (normal saline) was administered as a 20-mL IV infusion twice weekly on Days 1, 4, 8, 11, 15, 18, 22 and 25.	PF-05231023 100 mg n=2 Participants PF-05231023 100 mg was administered as a 20-mL IV infusion twice weekly on Days 1, 4, 8, 11, 15, 18, 22 and 25.
Number of Participants With Adverse Events (AEs)	2 Participants	2 Participants

PRIMARY outcome

Timeframe: Days -7 up to the last follow-up (Day 68)

Population: All participants who received at least 1 dose of study medication (PF-05231023 or placebo).

Vital signs included supine systolic blood pressure, diastolic blood pressure and pulse rate. Vital signs criteria of potential clinical concern were 1), blood pressure: systolic greater than or equal to (\>=)30 millimeters of mercury (mm Hg) change from baseline in the same posture or systolic less than (\<)90 mm Hg; diastolic \>=20 mm Hg change from baseline in the same posture or diastolic \<50 mm Hg; 2), Pulse rate: supine/Sitting: \<40 or greater than (\>) 120 beats per minute (bpm); Standing: \<40 or \>140 bpm.

Outcome measures

Outcome measures
Measure	Placebo n=2 Participants Placebo (normal saline) was administered as a 20-mL IV infusion twice weekly on Days 1, 4, 8, 11, 15, 18, 22 and 25.	PF-05231023 100 mg n=2 Participants PF-05231023 100 mg was administered as a 20-mL IV infusion twice weekly on Days 1, 4, 8, 11, 15, 18, 22 and 25.
Number of Participants With Vital Signs Data Met Criteria of Potential Clinical Concern	0 Participants	0 Participants

PRIMARY outcome

Timeframe: Days -7 up to the last follow-up (Day 68)

Population: All participants who received at least 1 dose of study medication (PF-05231023 or placebo).

ECG criteria of potential clinical concern were 1), PR interval:\>=300 msec, \>=25% increase when baseline \>200 msec, or \>=50% increase when baseline \<=200 msec; 2), QRS interval:\>=140 msec, or \>=50% increase from baseline; 3), QT interval corrected for heart rate (QTc)/QTc interval using Fridericia's formula (QTcF):\>=500 msec, QTcF interval: absolute value \>=450 - \<480 msec(borderline), \>=480 msec (prolonged), absolute change 30 - \<60 msec (borderline) or \>=60 msec (prolonged). 12-lead ECG (triplicate) was performed on Day 0 and 12-lead ECG (singlet) was performed at other times.

Outcome measures

Outcome measures
Measure	Placebo n=2 Participants Placebo (normal saline) was administered as a 20-mL IV infusion twice weekly on Days 1, 4, 8, 11, 15, 18, 22 and 25.	PF-05231023 100 mg n=2 Participants PF-05231023 100 mg was administered as a 20-mL IV infusion twice weekly on Days 1, 4, 8, 11, 15, 18, 22 and 25.
Number of Participants With Electrocardiogram (ECG) Data Met Criteria of Potential Clinical Concern	1 Participants	0 Participants

PRIMARY outcome

Timeframe: Days 1 up to the last follow-up (Day 68)

Population: All participants who received at least 1 dose of active study medication (PF-05231023). Neutralizing antibodies were not tested because all participants who received PF-05231023 100 mg tested negative for anti-PF-05231023 antibodies.

Anti-PF-05231023 antibodies were analyzed using a tiered testing strategy of screen, confirm, and titer characterization. Positive was defined as titer value \>=6.23 and negative was defined as titer value \<6.23. Samples tested positive were also to be analyzed in a neutralization assay to determine whether or not they were neutralizing or non-neutralizing.

Outcome measures

Outcome measures
Measure	Placebo n=2 Participants Placebo (normal saline) was administered as a 20-mL IV infusion twice weekly on Days 1, 4, 8, 11, 15, 18, 22 and 25.	PF-05231023 100 mg n=2 Participants PF-05231023 100 mg was administered as a 20-mL IV infusion twice weekly on Days 1, 4, 8, 11, 15, 18, 22 and 25.
Number of Participants With Positive Anti-PF-05231023 Antibodies and Neutralizing Antibodies.	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Days -7 up to the last follow-up (Day 68)

Population: All participants who received at least 1 dose of study medication (PF-05231023 or placebo).

The total number of participants with laboratory test abnormalities without regard to baseline abnormality was assessed.

Outcome measures

Outcome measures
Measure	Placebo n=2 Participants Placebo (normal saline) was administered as a 20-mL IV infusion twice weekly on Days 1, 4, 8, 11, 15, 18, 22 and 25.	PF-05231023 100 mg n=2 Participants PF-05231023 100 mg was administered as a 20-mL IV infusion twice weekly on Days 1, 4, 8, 11, 15, 18, 22 and 25.
Number of Participants With Abnormal Clinical Laboratory Measurements	0 Participants	0 Participants

Adverse Events

Placebo

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

PF-05231023 100 mg

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Additional Information

Pfizer ClinicalTrials.gov Call Center

Pfizer, Inc.

Phone: 1-800-718-1021

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.
Publication restrictions are in place

Restriction type: OTHER

Other adverse events
Measure	Placebo n=2 participants at risk Placebo (normal saline) was administered as a 20-mL IV infusion twice weekly on Days 1, 4, 8, 11, 15, 18, 22 and 25.	PF-05231023 100 mg n=2 participants at risk PF-05231023 100 mg was administered as a 20-mL IV infusion twice weekly on Days 1, 4, 8, 11, 15, 18, 22 and 25.
Gastrointestinal disorders Abdominal pain	0.00% 0/2 • Day -7 through Day 68 (AEs occurred after first dose of study drug were treatment-emergent). Serious AEs (SAEs) were reported from time that subject provided informed consent until 28 calendar days after last dose of the study drug. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	50.0% 1/2 • Day -7 through Day 68 (AEs occurred after first dose of study drug were treatment-emergent). Serious AEs (SAEs) were reported from time that subject provided informed consent until 28 calendar days after last dose of the study drug. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Diarrhoea	0.00% 0/2 • Day -7 through Day 68 (AEs occurred after first dose of study drug were treatment-emergent). Serious AEs (SAEs) were reported from time that subject provided informed consent until 28 calendar days after last dose of the study drug. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	50.0% 1/2 • Day -7 through Day 68 (AEs occurred after first dose of study drug were treatment-emergent). Serious AEs (SAEs) were reported from time that subject provided informed consent until 28 calendar days after last dose of the study drug. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Eructation	0.00% 0/2 • Day -7 through Day 68 (AEs occurred after first dose of study drug were treatment-emergent). Serious AEs (SAEs) were reported from time that subject provided informed consent until 28 calendar days after last dose of the study drug. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	50.0% 1/2 • Day -7 through Day 68 (AEs occurred after first dose of study drug were treatment-emergent). Serious AEs (SAEs) were reported from time that subject provided informed consent until 28 calendar days after last dose of the study drug. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Flatulence	50.0% 1/2 • Day -7 through Day 68 (AEs occurred after first dose of study drug were treatment-emergent). Serious AEs (SAEs) were reported from time that subject provided informed consent until 28 calendar days after last dose of the study drug. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/2 • Day -7 through Day 68 (AEs occurred after first dose of study drug were treatment-emergent). Serious AEs (SAEs) were reported from time that subject provided informed consent until 28 calendar days after last dose of the study drug. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Nausea	0.00% 0/2 • Day -7 through Day 68 (AEs occurred after first dose of study drug were treatment-emergent). Serious AEs (SAEs) were reported from time that subject provided informed consent until 28 calendar days after last dose of the study drug. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	50.0% 1/2 • Day -7 through Day 68 (AEs occurred after first dose of study drug were treatment-emergent). Serious AEs (SAEs) were reported from time that subject provided informed consent until 28 calendar days after last dose of the study drug. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
General disorders Chest pain	50.0% 1/2 • Day -7 through Day 68 (AEs occurred after first dose of study drug were treatment-emergent). Serious AEs (SAEs) were reported from time that subject provided informed consent until 28 calendar days after last dose of the study drug. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/2 • Day -7 through Day 68 (AEs occurred after first dose of study drug were treatment-emergent). Serious AEs (SAEs) were reported from time that subject provided informed consent until 28 calendar days after last dose of the study drug. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
General disorders Chills	0.00% 0/2 • Day -7 through Day 68 (AEs occurred after first dose of study drug were treatment-emergent). Serious AEs (SAEs) were reported from time that subject provided informed consent until 28 calendar days after last dose of the study drug. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	50.0% 1/2 • Day -7 through Day 68 (AEs occurred after first dose of study drug were treatment-emergent). Serious AEs (SAEs) were reported from time that subject provided informed consent until 28 calendar days after last dose of the study drug. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
General disorders Puncture site pain	50.0% 1/2 • Day -7 through Day 68 (AEs occurred after first dose of study drug were treatment-emergent). Serious AEs (SAEs) were reported from time that subject provided informed consent until 28 calendar days after last dose of the study drug. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/2 • Day -7 through Day 68 (AEs occurred after first dose of study drug were treatment-emergent). Serious AEs (SAEs) were reported from time that subject provided informed consent until 28 calendar days after last dose of the study drug. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Infections and infestations Upper respiratory tract infection	50.0% 1/2 • Day -7 through Day 68 (AEs occurred after first dose of study drug were treatment-emergent). Serious AEs (SAEs) were reported from time that subject provided informed consent until 28 calendar days after last dose of the study drug. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/2 • Day -7 through Day 68 (AEs occurred after first dose of study drug were treatment-emergent). Serious AEs (SAEs) were reported from time that subject provided informed consent until 28 calendar days after last dose of the study drug. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Injury, poisoning and procedural complications Laceration	0.00% 0/2 • Day -7 through Day 68 (AEs occurred after first dose of study drug were treatment-emergent). Serious AEs (SAEs) were reported from time that subject provided informed consent until 28 calendar days after last dose of the study drug. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	50.0% 1/2 • Day -7 through Day 68 (AEs occurred after first dose of study drug were treatment-emergent). Serious AEs (SAEs) were reported from time that subject provided informed consent until 28 calendar days after last dose of the study drug. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Injury, poisoning and procedural complications Wound	0.00% 0/2 • Day -7 through Day 68 (AEs occurred after first dose of study drug were treatment-emergent). Serious AEs (SAEs) were reported from time that subject provided informed consent until 28 calendar days after last dose of the study drug. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	50.0% 1/2 • Day -7 through Day 68 (AEs occurred after first dose of study drug were treatment-emergent). Serious AEs (SAEs) were reported from time that subject provided informed consent until 28 calendar days after last dose of the study drug. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Nervous system disorders Headache	50.0% 1/2 • Day -7 through Day 68 (AEs occurred after first dose of study drug were treatment-emergent). Serious AEs (SAEs) were reported from time that subject provided informed consent until 28 calendar days after last dose of the study drug. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/2 • Day -7 through Day 68 (AEs occurred after first dose of study drug were treatment-emergent). Serious AEs (SAEs) were reported from time that subject provided informed consent until 28 calendar days after last dose of the study drug. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Nervous system disorders Hypoaesthesia	0.00% 0/2 • Day -7 through Day 68 (AEs occurred after first dose of study drug were treatment-emergent). Serious AEs (SAEs) were reported from time that subject provided informed consent until 28 calendar days after last dose of the study drug. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	50.0% 1/2 • Day -7 through Day 68 (AEs occurred after first dose of study drug were treatment-emergent). Serious AEs (SAEs) were reported from time that subject provided informed consent until 28 calendar days after last dose of the study drug. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Psychiatric disorders Middle insomnia	50.0% 1/2 • Day -7 through Day 68 (AEs occurred after first dose of study drug were treatment-emergent). Serious AEs (SAEs) were reported from time that subject provided informed consent until 28 calendar days after last dose of the study drug. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/2 • Day -7 through Day 68 (AEs occurred after first dose of study drug were treatment-emergent). Serious AEs (SAEs) were reported from time that subject provided informed consent until 28 calendar days after last dose of the study drug. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Respiratory, thoracic and mediastinal disorders Cough	0.00% 0/2 • Day -7 through Day 68 (AEs occurred after first dose of study drug were treatment-emergent). Serious AEs (SAEs) were reported from time that subject provided informed consent until 28 calendar days after last dose of the study drug. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	50.0% 1/2 • Day -7 through Day 68 (AEs occurred after first dose of study drug were treatment-emergent). Serious AEs (SAEs) were reported from time that subject provided informed consent until 28 calendar days after last dose of the study drug. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Respiratory, thoracic and mediastinal disorders Dyspnoea	50.0% 1/2 • Day -7 through Day 68 (AEs occurred after first dose of study drug were treatment-emergent). Serious AEs (SAEs) were reported from time that subject provided informed consent until 28 calendar days after last dose of the study drug. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/2 • Day -7 through Day 68 (AEs occurred after first dose of study drug were treatment-emergent). Serious AEs (SAEs) were reported from time that subject provided informed consent until 28 calendar days after last dose of the study drug. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Respiratory, thoracic and mediastinal disorders Nasal congestion	0.00% 0/2 • Day -7 through Day 68 (AEs occurred after first dose of study drug were treatment-emergent). Serious AEs (SAEs) were reported from time that subject provided informed consent until 28 calendar days after last dose of the study drug. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	50.0% 1/2 • Day -7 through Day 68 (AEs occurred after first dose of study drug were treatment-emergent). Serious AEs (SAEs) were reported from time that subject provided informed consent until 28 calendar days after last dose of the study drug. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Injury, poisoning and procedural complications Contusion	0.00% 0/2 • Day -7 through Day 68 (AEs occurred after first dose of study drug were treatment-emergent). Serious AEs (SAEs) were reported from time that subject provided informed consent until 28 calendar days after last dose of the study drug. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	50.0% 1/2 • Day -7 through Day 68 (AEs occurred after first dose of study drug were treatment-emergent). Serious AEs (SAEs) were reported from time that subject provided informed consent until 28 calendar days after last dose of the study drug. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Musculoskeletal and connective tissue disorders Pain in extremity	0.00% 0/2 • Day -7 through Day 68 (AEs occurred after first dose of study drug were treatment-emergent). Serious AEs (SAEs) were reported from time that subject provided informed consent until 28 calendar days after last dose of the study drug. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	50.0% 1/2 • Day -7 through Day 68 (AEs occurred after first dose of study drug were treatment-emergent). Serious AEs (SAEs) were reported from time that subject provided informed consent until 28 calendar days after last dose of the study drug. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.