Trial Outcomes & Findings for A Bioequivalence Study Comparing A Fixed Dose Combination Formulation Of Myrin P Forte That Contains Rifampicin, Isoniazid, Ethambutol And Pyrazinamide Per Tablet To An Equivalent Dose Of Single Drug Reference Preparations Of Similar Combination Following Oral Administration In Healthy Adults (NCT NCT01399788)

Last Updated: 2017-04-05

Results Overview

Area under the plasma concentration-time curve from time zero (pre-dose) to the time of last measured concentration (AUClast).

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

36 participants

Primary outcome timeframe

0 (pre-dose), 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16 and 24 hours (hrs) post-dose

Results posted on

2017-04-05

Participant Flow

Participant milestones

Participant milestones
Measure	Myrin-P Forte First, Then Four Single Drug References Single oral dose of 4 fixed dose combination (FDC) tablets of Myrin-P Forte (each tablet contains 150 milligram (mg) rifampicin, 75 mg isoniazid, 275 mg ethambutol and 400 mg pyrazinamide) in first intervention period; and single oral dose of 4 reference products: 600 mg rifampicin capsules, 300 mg isoniazid, 1100 mg ethambutol and 1500 mg pyrazinamide tablets in second intervention period. A washout period of at least 1 week was maintained between each period.	Four Single Drug References First, Then Myrin-P Forte Single oral dose of 4 reference products: 600 mg rifampicin capsules, 300 mg isoniazid, 1100 mg ethambutol and 1500 mg pyrazinamide tablets in first intervention period; and single oral dose of 4 FDC tablets of Myrin-P Forte (each tablet contains 150 mg rifampicin, 75 mg isoniazid, 275 mg ethambutol and 400 mg pyrazinamide) in second intervention period. A washout period of at least 1 week was maintained between each period.
First Intervention Period STARTED	18	18
First Intervention Period COMPLETED	17	18
First Intervention Period NOT COMPLETED	1	0
Washout Period (at Least 1 Week) STARTED	17	18
Washout Period (at Least 1 Week) COMPLETED	17	18
Washout Period (at Least 1 Week) NOT COMPLETED	0	0
Second Intervention Period STARTED	17	18
Second Intervention Period COMPLETED	17	18
Second Intervention Period NOT COMPLETED	0	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Myrin-P Forte First, Then Four Single Drug References Single oral dose of 4 fixed dose combination (FDC) tablets of Myrin-P Forte (each tablet contains 150 milligram (mg) rifampicin, 75 mg isoniazid, 275 mg ethambutol and 400 mg pyrazinamide) in first intervention period; and single oral dose of 4 reference products: 600 mg rifampicin capsules, 300 mg isoniazid, 1100 mg ethambutol and 1500 mg pyrazinamide tablets in second intervention period. A washout period of at least 1 week was maintained between each period.	Four Single Drug References First, Then Myrin-P Forte Single oral dose of 4 reference products: 600 mg rifampicin capsules, 300 mg isoniazid, 1100 mg ethambutol and 1500 mg pyrazinamide tablets in first intervention period; and single oral dose of 4 FDC tablets of Myrin-P Forte (each tablet contains 150 mg rifampicin, 75 mg isoniazid, 275 mg ethambutol and 400 mg pyrazinamide) in second intervention period. A washout period of at least 1 week was maintained between each period.
First Intervention Period Adverse Event	1	0

Baseline Characteristics

A Bioequivalence Study Comparing A Fixed Dose Combination Formulation Of Myrin P Forte That Contains Rifampicin, Isoniazid, Ethambutol And Pyrazinamide Per Tablet To An Equivalent Dose Of Single Drug Reference Preparations Of Similar Combination Following Oral Administration In Healthy Adults

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Entire Study Population n=36 Participants Includes participants randomized to receive Myrin-P Forte first and four single drug references first.
Age, Continuous	32.6 years STANDARD_DEVIATION 8.8 • n=99 Participants
Sex: Female, Male Female	2 Participants n=99 Participants
Sex: Female, Male Male	34 Participants n=99 Participants

PRIMARY outcome

Timeframe: 0 (pre-dose), 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16 and 24 hours (hrs) post-dose

Population: Pharmacokinetic (PK) parameter analysis population included all randomized and treated participants who had at least 1 of the PK parameters for one of four analytes in at least 1 treatment period.

Area under the plasma concentration-time curve from time zero (pre-dose) to the time of last measured concentration (AUClast).

Outcome measures

Outcome measures
Measure	Myrin-P Forte n=36 Participants Single oral dose of 4 FDC tablets of Myrin-P Forte (Test) in either first intervention period or second intervention period. Each tablet contains 150 mg rifampicin, 75 mg isoniazid, 275 mg ethambutol and 400 mg pyrazinamide.	Four Single Drug References n=35 Participants Single oral dose of 4 reference products: 600 mg rifampicin capsules, 300 mg isoniazid, 1100 mg ethambutol and 1500 mg pyrazinamide tablets in either first intervention period or second intervention period.
Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) Rifampicin	79360.0 ng*hr/mL Standard Deviation 29613.0	77180.0 ng*hr/mL Standard Deviation 20516.0
Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) Isoniazid	20550.0 ng*hr/mL Standard Deviation 12920.0	18800.0 ng*hr/mL Standard Deviation 12941.0
Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) Ethambutol	15070.0 ng*hr/mL Standard Deviation 3298.8	15170.0 ng*hr/mL Standard Deviation 3119.1

PRIMARY outcome

Timeframe: 0 (pre-dose), 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16 and 24 hrs post-dose

Population: PK parameter analysis population included all randomized and treated participants who had at least 1 of the PK parameters for one of four analytes in at least 1 treatment period.

Outcome measures

Outcome measures
Measure	Myrin-P Forte n=36 Participants Single oral dose of 4 FDC tablets of Myrin-P Forte (Test) in either first intervention period or second intervention period. Each tablet contains 150 mg rifampicin, 75 mg isoniazid, 275 mg ethambutol and 400 mg pyrazinamide.	Four Single Drug References n=35 Participants Single oral dose of 4 reference products: 600 mg rifampicin capsules, 300 mg isoniazid, 1100 mg ethambutol and 1500 mg pyrazinamide tablets in either first intervention period or second intervention period.
Maximum Observed Plasma Concentration (Cmax) Rifampicin	12120.0 ng/mL Standard Deviation 3682.3	11830.0 ng/mL Standard Deviation 2351.8
Maximum Observed Plasma Concentration (Cmax) Isoniazid	4418.0 ng/mL Standard Deviation 1619.0	4237.0 ng/mL Standard Deviation 1658.9
Maximum Observed Plasma Concentration (Cmax) Ethambutol	2771.0 ng/mL Standard Deviation 825.4	2865.0 ng/mL Standard Deviation 950.5

PRIMARY outcome

Timeframe: 0 (pre-dose), 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, 36 and 48 hrs post-dose

Population: PK parameter analysis population included all randomized and treated participants who had at least 1 of the PK parameters for one of four analytes in at least 1 treatment period.

AUClast\[dn\] = Dose normalized area under the plasma concentration-time curve (AUC\[dn\]) from time zero (pre-dose) to the time of last measured concentration. It is obtained from AUClast divided by dose and then multiplied by 1500. The test and reference for pyrazinamide were given at different doses, so dose-normalized parameters were used for analysis for adjusting the dose effect on bioequivalence conclusion.

Outcome measures

Outcome measures
Measure	Myrin-P Forte n=36 Participants Single oral dose of 4 FDC tablets of Myrin-P Forte (Test) in either first intervention period or second intervention period. Each tablet contains 150 mg rifampicin, 75 mg isoniazid, 275 mg ethambutol and 400 mg pyrazinamide.	Four Single Drug References n=35 Participants Single oral dose of 4 reference products: 600 mg rifampicin capsules, 300 mg isoniazid, 1100 mg ethambutol and 1500 mg pyrazinamide tablets in either first intervention period or second intervention period.
Dose Normalized Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast[dn]) for Pyrazinamide	453500 (ng*hr/mL)/mg Standard Deviation 76250	447900 (ng*hr/mL)/mg Standard Deviation 82578

PRIMARY outcome

Timeframe: 0 (pre-dose), 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, 36 and 48 hrs post-dose

Population: PK parameter analysis population included all randomized and treated participants who had at least 1 of the PK parameters for one of four analytes in at least 1 treatment period.

It is obtained from Cmax divided by dose and then multiplied by 1500. The test and reference for pyrazinamide were given at different doses, so dose-normalized parameters were used for analysis for adjusting the dose effect on bioequivalence conclusion.

Outcome measures

Outcome measures
Measure	Myrin-P Forte n=36 Participants Single oral dose of 4 FDC tablets of Myrin-P Forte (Test) in either first intervention period or second intervention period. Each tablet contains 150 mg rifampicin, 75 mg isoniazid, 275 mg ethambutol and 400 mg pyrazinamide.	Four Single Drug References n=35 Participants Single oral dose of 4 reference products: 600 mg rifampicin capsules, 300 mg isoniazid, 1100 mg ethambutol and 1500 mg pyrazinamide tablets in either first intervention period or second intervention period.
Dose Normalized Maximum Observed Plasma Concentration (Cmax[dn]) for Pyrazinamide	33890.0 (ng/mL)/mg Standard Deviation 6490.2	35580.0 (ng/mL)/mg Standard Deviation 12134.0

SECONDARY outcome

Timeframe: 0 (pre-dose), 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16 and 24 hrs post-dose

Population: PK parameter analysis population included all randomized and treated participants who had at least 1 of the PK parameters for one of four analytes in at least 1 treatment period. Here, 'n' is number of participants who were evaluable for this measure.

AUC (0-∞) = Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0-∞). It is obtained from AUC (0-t) plus AUC (t-∞).

Outcome measures

Outcome measures
Measure	Myrin-P Forte n=36 Participants Single oral dose of 4 FDC tablets of Myrin-P Forte (Test) in either first intervention period or second intervention period. Each tablet contains 150 mg rifampicin, 75 mg isoniazid, 275 mg ethambutol and 400 mg pyrazinamide.	Four Single Drug References n=35 Participants Single oral dose of 4 reference products: 600 mg rifampicin capsules, 300 mg isoniazid, 1100 mg ethambutol and 1500 mg pyrazinamide tablets in either first intervention period or second intervention period.
Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUC[0-∞]) Rifampicin (n= 36, 35)	80940.0 ng*hr/mL Standard Deviation 34613.0	78400.0 ng*hr/mL Standard Deviation 22226.0
Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUC[0-∞]) Isoniazid (n= 35, 35)	21210.0 ng*hr/mL Standard Deviation 13562.0	19460.0 ng*hr/mL Standard Deviation 14171.0
Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUC[0-∞]) Ethambutol (n= 28, 31)	17150.0 ng*hr/mL Standard Deviation 3362.1	17050.0 ng*hr/mL Standard Deviation 3378.9

SECONDARY outcome

Timeframe: 0 (pre-dose), 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, 36 and 48 hrs post-dose

Population: PK parameter analysis population included all randomized and treated participants who had at least 1 of the PK parameters for one of four analytes in at least 1 treatment period.

AUC \[0-∞\]\[dn\] = Dose normalized area under the plasma concentration versus time curve (AUC\[dn\]) from time zero (pre-dose) to extrapolated infinite time (0-∞). It is obtained from AUC (0-∞) divided by dose and then multiplied by 1500. The test and reference for pyrazinamide were given at different doses, so dose-normalized parameters were used for analysis for adjusting the dose effect on bioequivalence conclusion.

Outcome measures

Outcome measures
Measure	Myrin-P Forte n=36 Participants Single oral dose of 4 FDC tablets of Myrin-P Forte (Test) in either first intervention period or second intervention period. Each tablet contains 150 mg rifampicin, 75 mg isoniazid, 275 mg ethambutol and 400 mg pyrazinamide.	Four Single Drug References n=35 Participants Single oral dose of 4 reference products: 600 mg rifampicin capsules, 300 mg isoniazid, 1100 mg ethambutol and 1500 mg pyrazinamide tablets in either first intervention period or second intervention period.
Dose Normalized Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUC [0-∞][dn]) for Pyrazinamide	471000 (ng*hr/mL)/mg Standard Deviation 85153	464800 (ng*hr/mL)/mg Standard Deviation 92222

SECONDARY outcome

Timeframe: 0 (pre-dose), 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16 and 24 hrs post-dose for rifampicin, isoniazid and ethambutol and additional 36 and 48 hrs post-dose for pyrazinamide

Plasma decay half-life is the time measured for the plasma concentration to decrease by one half.

Outcome measures

Outcome measures
Measure	Myrin-P Forte n=36 Participants Single oral dose of 4 FDC tablets of Myrin-P Forte (Test) in either first intervention period or second intervention period. Each tablet contains 150 mg rifampicin, 75 mg isoniazid, 275 mg ethambutol and 400 mg pyrazinamide.	Four Single Drug References n=35 Participants Single oral dose of 4 reference products: 600 mg rifampicin capsules, 300 mg isoniazid, 1100 mg ethambutol and 1500 mg pyrazinamide tablets in either first intervention period or second intervention period.
Plasma Decay Half-life (t1/2) Rifampicin (n= 36, 35)	3.6630 hr Standard Deviation 1.0477	3.4290 hr Standard Deviation 0.6938
Plasma Decay Half-life (t1/2) Isoniazid (n= 35, 35)	3.7340 hr Standard Deviation 0.9197	3.9470 hr Standard Deviation 1.1751
Plasma Decay Half-life (t1/2) Ethambutol (n= 28, 31)	7.7430 hr Standard Deviation 1.1716	7.6390 hr Standard Deviation 1.1158
Plasma Decay Half-life (t1/2) Pyrazinamide (n= 36, 35)	9.8630 hr Standard Deviation 1.3333	9.7660 hr Standard Deviation 1.3671

SECONDARY outcome

Timeframe: 0 (pre-dose), 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16 and 24 hrs post-dose for rifampicin, isoniazid and ethambutol and additional 36 and 48 hrs post-dose for pyrazinamide

Population: PK parameter analysis population included all randomized and treated participants who had at least 1 of the PK parameters for one of four analytes in at least 1 treatment period.

Outcome measures

Outcome measures
Measure	Myrin-P Forte n=36 Participants Single oral dose of 4 FDC tablets of Myrin-P Forte (Test) in either first intervention period or second intervention period. Each tablet contains 150 mg rifampicin, 75 mg isoniazid, 275 mg ethambutol and 400 mg pyrazinamide.	Four Single Drug References n=35 Participants Single oral dose of 4 reference products: 600 mg rifampicin capsules, 300 mg isoniazid, 1100 mg ethambutol and 1500 mg pyrazinamide tablets in either first intervention period or second intervention period.
Time to Reach Maximum Observed Plasma Concentration (Tmax) Rifampicin	2.00 hr Interval 1.0 to 4.0	1.50 hr Interval 1.0 to 3.0
Time to Reach Maximum Observed Plasma Concentration (Tmax) Isoniazid	1.02 hr Interval 0.25 to 2.52	1.00 hr Interval 0.25 to 3.0
Time to Reach Maximum Observed Plasma Concentration (Tmax) Ethambutol	2.77 hr Interval 1.0 to 4.28	2.48 hr Interval 1.5 to 4.0
Time to Reach Maximum Observed Plasma Concentration (Tmax) Pyrazinamide	1.50 hr Interval 0.25 to 3.02	1.50 hr Interval 0.25 to 6.0

Adverse Events

Myrin-P Forte

Serious events: 0 serious events

Other events: 34 other events

Deaths: 0 deaths

Four Single Drug References

Serious events: 0 serious events

Other events: 31 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
Publication restrictions are in place

Measure	Myrin-P Forte n=36 participants at risk Single oral dose of 4 FDC tablets of Myrin-P Forte (Test) in either first intervention period or second intervention period. Each tablet contains 150 mg rifampicin, 75 mg isoniazid, 275 mg ethambutol and 400 mg pyrazinamide.	Four Single Drug References n=35 participants at risk Single oral dose of 4 reference products: 600 mg rifampicin capsules, 300 mg isoniazid, 1100 mg ethambutol and 1500 mg pyrazinamide tablets in either first intervention period or second intervention period.
Gastrointestinal disorders Abdominal pain	2.8% 1/36 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% 0/35 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	2.8% 1/36 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% 0/35 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	2.8% 1/36 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% 0/35 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 Catheter site swelling	2.8% 1/36 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% 0/35 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 Pyrexia	2.8% 1/36 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% 0/35 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 Oral herpes	2.8% 1/36 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% 0/35 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	2.8% 1/36 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% 0/35 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.
Investigations Blood glucose increased	2.8% 1/36 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.	2.9% 1/35 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.
Investigations Cardiac murmur functional	0.00% 0/36 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.	2.9% 1/35 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 Dizziness	0.00% 0/36 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.	2.9% 1/35 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	2.8% 1/36 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% 0/35 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.
Renal and urinary disorders Chromaturia	88.9% 32/36 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.	88.6% 31/35 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 Oropharyngeal pain	0.00% 0/36 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.	2.9% 1/35 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 Rhinorrhoea	2.8% 1/36 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% 0/35 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.
Skin and subcutaneous tissue disorders Dermatitis contact	2.8% 1/36 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.	2.9% 1/35 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.
Skin and subcutaneous tissue disorders Drug eruption	2.8% 1/36 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.	2.9% 1/35 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.