Trial Outcomes & Findings for Drug-Drug Interaction Study: ASP2151 and Ritonavir (NCT NCT02223351)

NCT ID: NCT02223351

Last Updated: 2019-02-27

Results Overview

• Recruitment status: COMPLETED
• Study phase: PHASE1
• Target enrollment: 48 participants
• Primary outcome timeframe: Blood samples were taken at pre-dose of Day 1 and 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48 and 72h after post doses in first or second intervention
• Results posted on: 2019-02-27

Participant Flow

Participants took part in the study at one investigative site in United Kingdom from 05-September 2014 to 04-December 2014

Participant milestones

Measure	400mg ASP2151 ASP2151 400mg alone followed by ASP2151 400mg + 600 mg ritonavir, or vice versa.	1200mg ASP2151 ASP2151 1200mg alone followed by ASP2151 1200mg + 600 mg ritonavir, or vice versa.
Overall Study STARTED	24	24
Overall Study First Intervention (8 Days)	24	24
Overall Study Wasout (2weeks)	24	24
Overall Study Second Intervention (8 Days)	24	24
Overall Study COMPLETED	24	24
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Drug-Drug Interaction Study: ASP2151 and Ritonavir

Baseline characteristics by cohort

Measure	400mg ASP2151 n=24 Participants ASP2151 400mg alone followed by ASP2151 400mg + 600 mg ritonavir, or vice versa.	1200mg ASP2151 n=24 Participants ASP2151 1200mg alone followed by ASP2151 1200mg + 600 mg ritonavir, or vice versa.	Total n=48 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	24 Participants n=5 Participants	23 Participants n=7 Participants	47 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Continuous	28.2 year STANDARD_DEVIATION 6.4 • n=5 Participants	27 year STANDARD_DEVIATION 4.9 • n=7 Participants	27.6 year STANDARD_DEVIATION 5.7 • n=5 Participants
Sex: Female, Male Female	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Sex: Female, Male Male	24 Participants n=5 Participants	24 Participants n=7 Participants	48 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	3 Participants n=5 Participants	0 Participants n=7 Participants	3 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	21 Participants n=5 Participants	24 Participants n=7 Participants	45 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	1 Participants n=5 Participants	3 Participants n=7 Participants	4 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	4 Participants n=5 Participants	5 Participants n=7 Participants	9 Participants n=5 Participants
Race (NIH/OMB) White	17 Participants n=5 Participants	15 Participants n=7 Participants	32 Participants n=5 Participants
Race (NIH/OMB) More than one race	2 Participants n=5 Participants	1 Participants n=7 Participants	3 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Region of Enrollment United Kingdom	24 Participants n=5 Participants	24 Participants n=7 Participants	48 Participants n=5 Participants

PRIMARY outcome

Timeframe: Blood samples were taken at pre-dose of Day 1 and 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48 and 72h after post doses in first or second intervention

Outcome measures

Measure	400 mg ASP2151 Alone n=24 Participants ASP2151(400 mg) alone	400mg ASP2151 With Ritonavir n=24 Participants 400mg ASP2151 alone followed by 400mg ASP2151 + 600mg ritonavir ASP2151 ritonavir	1200 mg ASP2151 Alone n=24 Participants ASP2151(1200 mg) alone	1200mg ASP2151 With Ritonavir n=24 Participants 1200mg ASP2151 alone followed by 1200mg ASP2151 + 600mg ritonavir ASP2151 ritonavir
Peak Plasma Concentration (Cmax) of ASP2151	1845.7 ng/mL Geometric Coefficient of Variation 25.4	2518.7 ng/mL Geometric Coefficient of Variation 21.9	3804 ng/mL Geometric Coefficient of Variation 28.8	6211.6 ng/mL Geometric Coefficient of Variation 29.2

PRIMARY outcome

Timeframe: Blood samples were taken at pre-dose of Day 1 and 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48 and 72h after post doses in first or second intervention

Outcome measures

Measure	400 mg ASP2151 Alone n=24 Participants ASP2151(400 mg) alone	400mg ASP2151 With Ritonavir n=24 Participants 400mg ASP2151 alone followed by 400mg ASP2151 + 600mg ritonavir ASP2151 ritonavir	1200 mg ASP2151 Alone n=24 Participants ASP2151(1200 mg) alone	1200mg ASP2151 With Ritonavir n=24 Participants 1200mg ASP2151 alone followed by 1200mg ASP2151 + 600mg ritonavir ASP2151 ritonavir
Time of Peak Concentration (Tmax) of ASP2151	3 h Interval 1.0 to 4.0	4 h Interval 1.0 to 10.0	3.025 h Interval 1.0 to 4.12	4 h Interval 2.0 to 12.0

PRIMARY outcome

Timeframe: Blood samples were taken at pre-dose of Day 1 and 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48 and 72h after post doses in first or second intervention

Outcome measures

Measure	400 mg ASP2151 Alone n=24 Participants ASP2151(400 mg) alone	400mg ASP2151 With Ritonavir n=24 Participants 400mg ASP2151 alone followed by 400mg ASP2151 + 600mg ritonavir ASP2151 ritonavir	1200 mg ASP2151 Alone n=24 Participants ASP2151(1200 mg) alone	1200mg ASP2151 With Ritonavir n=24 Participants 1200mg ASP2151 alone followed by 1200mg ASP2151 + 600mg ritonavir ASP2151 ritonavir
Area Under the Curve (AUC) of ASP2151	23162.4 h*ng/mL Geometric Coefficient of Variation 34.2	60225.3 h*ng/mL Geometric Coefficient of Variation 23	48532.3 h*ng/mL Geometric Coefficient of Variation 29.3	162131.6 h*ng/mL Geometric Coefficient of Variation 25.3

PRIMARY outcome

Timeframe: Blood samples were taken at pre-dose of Day 1 and 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48 and 72h after post doses in first or second intervention

Outcome measures

Measure	400 mg ASP2151 Alone n=24 Participants ASP2151(400 mg) alone	400mg ASP2151 With Ritonavir n=24 Participants 400mg ASP2151 alone followed by 400mg ASP2151 + 600mg ritonavir ASP2151 ritonavir	1200 mg ASP2151 Alone n=24 Participants ASP2151(1200 mg) alone	1200mg ASP2151 With Ritonavir n=24 Participants 1200mg ASP2151 alone followed by 1200mg ASP2151 + 600mg ritonavir ASP2151 ritonavir
Half-Life (t1/2) of ASP2151	7.375 h Geometric Coefficient of Variation 14.9	12.575 h Geometric Coefficient of Variation 15.9	7.178 h Geometric Coefficient of Variation 17.5	12.498 h Geometric Coefficient of Variation 19.6

PRIMARY outcome

Timeframe: Blood samples were taken at pre-dose of Day 1 and 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48 and 72h after post doses in first or second intervention

Outcome measures

Measure	400 mg ASP2151 Alone n=24 Participants ASP2151(400 mg) alone	400mg ASP2151 With Ritonavir n=24 Participants 400mg ASP2151 alone followed by 400mg ASP2151 + 600mg ritonavir ASP2151 ritonavir	1200 mg ASP2151 Alone n=24 Participants ASP2151(1200 mg) alone	1200mg ASP2151 With Ritonavir n=24 Participants 1200mg ASP2151 alone followed by 1200mg ASP2151 + 600mg ritonavir ASP2151 ritonavir
Apparent Total Body Clearance (CL/F) of ASP2151 From Plasma	18.314 L/h Standard Deviation 7.2654	6.815 L/h Standard Deviation 1.6607	25.735 L/h Standard Deviation 7.5753	7.63 L/h Standard Deviation 1.9843

PRIMARY outcome

Timeframe: Blood samples were taken at pre-dose of Day 1 and 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48 and 72h after post doses in first or second intervention

Outcome measures

Measure	400 mg ASP2151 Alone n=24 Participants ASP2151(400 mg) alone	400mg ASP2151 With Ritonavir n=24 Participants 400mg ASP2151 alone followed by 400mg ASP2151 + 600mg ritonavir ASP2151 ritonavir	1200 mg ASP2151 Alone n=24 Participants ASP2151(1200 mg) alone	1200mg ASP2151 With Ritonavir n=24 Participants 1200mg ASP2151 alone followed by 1200mg ASP2151 + 600mg ritonavir ASP2151 ritonavir
Apparent Volume of Distribution (Vd/F) of ASP2151	190.1 L Standard Deviation 56.912	123.17 L Standard Deviation 28.366	266.33 L Standard Deviation 79.948	139.33 L Standard Deviation 43.231

SECONDARY outcome

Timeframe: Up to 31 days

Refer to the result of adverse event.

Outcome measures

Measure	400 mg ASP2151 Alone n=24 Participants ASP2151(400 mg) alone	400mg ASP2151 With Ritonavir n=24 Participants 400mg ASP2151 alone followed by 400mg ASP2151 + 600mg ritonavir ASP2151 ritonavir	1200 mg ASP2151 Alone n=24 Participants ASP2151(1200 mg) alone	1200mg ASP2151 With Ritonavir n=24 Participants 1200mg ASP2151 alone followed by 1200mg ASP2151 + 600mg ritonavir ASP2151 ritonavir
Number of Participants With Serious and Non-Serious Adverse Events Non-serious adverse event	8 participants	17 participants	15 participants	13 participants
Number of Participants With Serious and Non-Serious Adverse Events serious adverse event	0 participants	0 participants	0 participants	0 participants

OTHER_PRE_SPECIFIED outcome

Timeframe: Blood samples were taken at pre-dose of Day 1 and 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48 and 72h after post doses in first or second intervention

ASP1955888-00 is a metabolite of the study drug (ASP2151)

Outcome measures

Measure	400 mg ASP2151 Alone n=24 Participants ASP2151(400 mg) alone	400mg ASP2151 With Ritonavir n=24 Participants 400mg ASP2151 alone followed by 400mg ASP2151 + 600mg ritonavir ASP2151 ritonavir	1200 mg ASP2151 Alone n=24 Participants ASP2151(1200 mg) alone	1200mg ASP2151 With Ritonavir n=24 Participants 1200mg ASP2151 alone followed by 1200mg ASP2151 + 600mg ritonavir ASP2151 ritonavir
Peak Plasma Concentration (Cmax) of ASP1955888-00	189.9 ng/mL Geometric Coefficient of Variation 27.7	21.6 ng/mL Geometric Coefficient of Variation 70.7	421.5 ng/mL Geometric Coefficient of Variation 36.7	56.2 ng/mL Geometric Coefficient of Variation 79.9

OTHER_PRE_SPECIFIED outcome

Timeframe: Blood samples were taken at pre-dose of Day 1 and 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48 and 72h after post doses in first or second intervention

ASP1955888-00 is a metabolite of the study drug (ASP2151)

Outcome measures

Measure	400 mg ASP2151 Alone n=24 Participants ASP2151(400 mg) alone	400mg ASP2151 With Ritonavir n=24 Participants 400mg ASP2151 alone followed by 400mg ASP2151 + 600mg ritonavir ASP2151 ritonavir	1200 mg ASP2151 Alone n=24 Participants ASP2151(1200 mg) alone	1200mg ASP2151 With Ritonavir n=24 Participants 1200mg ASP2151 alone followed by 1200mg ASP2151 + 600mg ritonavir ASP2151 ritonavir
Time of Peak Concentration (Tmax) of ASP1955888-00	3 h Interval 1.0 to 4.07	1.5 h Interval 1.0 to 12.07	3 h Interval 1.98 to 6.0	1.01 h Interval 0.5 to 23.98

OTHER_PRE_SPECIFIED outcome

Timeframe: Blood samples were taken at pre-dose of Day 1 and 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48 and 72h after post doses in first or second intervention

ASP1955888-00 is a metabolite of the study drug (ASP2151)

Outcome measures

Measure	400 mg ASP2151 Alone n=24 Participants ASP2151(400 mg) alone	400mg ASP2151 With Ritonavir n=24 Participants 400mg ASP2151 alone followed by 400mg ASP2151 + 600mg ritonavir ASP2151 ritonavir	1200 mg ASP2151 Alone n=24 Participants ASP2151(1200 mg) alone	1200mg ASP2151 With Ritonavir n=24 Participants 1200mg ASP2151 alone followed by 1200mg ASP2151 + 600mg ritonavir ASP2151 ritonavir
Area Under the Curve (AUC) of ASP1955888-00	2636.2 h*ng/mL Geometric Coefficient of Variation 25.8	744.4 h*ng/mL Geometric Coefficient of Variation 12	6023.1 h*ng/mL Geometric Coefficient of Variation 30.2	1646.1 h*ng/mL Geometric Coefficient of Variation 37.3

OTHER_PRE_SPECIFIED outcome

Timeframe: Blood samples were taken at pre-dose of Day 1 and 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48 and 72h after post doses in first or second intervention

ASP1955888-00 is a metabolite of the study drug (ASP2151)

Outcome measures

Measure	400 mg ASP2151 Alone n=24 Participants ASP2151(400 mg) alone	400mg ASP2151 With Ritonavir n=24 Participants 400mg ASP2151 alone followed by 400mg ASP2151 + 600mg ritonavir ASP2151 ritonavir	1200 mg ASP2151 Alone n=24 Participants ASP2151(1200 mg) alone	1200mg ASP2151 With Ritonavir n=24 Participants 1200mg ASP2151 alone followed by 1200mg ASP2151 + 600mg ritonavir ASP2151 ritonavir
Half-life (t1/2) of ASP1955888-00	8.063 h Geometric Coefficient of Variation 18.1	40.213 h Geometric Coefficient of Variation 56.6	7.617 h Geometric Coefficient of Variation 18.6	42.197 h Geometric Coefficient of Variation 69.1

OTHER_PRE_SPECIFIED outcome

Timeframe: Blood samples were taken at pre-dose of Day 1 and 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48 and 72h after post doses in first or second intervention

ASP1955888-00 is a metabolite of the study drug (ASP2151)

Outcome measures

Measure	400 mg ASP2151 Alone n=24 Participants ASP2151(400 mg) alone	400mg ASP2151 With Ritonavir n=24 Participants 400mg ASP2151 alone followed by 400mg ASP2151 + 600mg ritonavir ASP2151 ritonavir	1200 mg ASP2151 Alone n=24 Participants ASP2151(1200 mg) alone	1200mg ASP2151 With Ritonavir n=24 Participants 1200mg ASP2151 alone followed by 1200mg ASP2151 + 600mg ritonavir ASP2151 ritonavir
Apparent Total Body Clearance (CL/F) From Plasma of ASP1955888-00	156.72 L/h Standard Deviation 43.197	540.93 L/h Standard Deviation 68.554	207.45 L/h Standard Deviation 59.311	775.35 L/h Standard Deviation 315.166

OTHER_PRE_SPECIFIED outcome

Timeframe: Blood samples were taken at pre-dose of Day 1 and 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48 and 72h after post doses in first or second intervention

ASP1955888-00 is a metabolite of the study drug (ASP2151)

Outcome measures

Measure	400 mg ASP2151 Alone n=24 Participants ASP2151(400 mg) alone	400mg ASP2151 With Ritonavir n=24 Participants 400mg ASP2151 alone followed by 400mg ASP2151 + 600mg ritonavir ASP2151 ritonavir	1200 mg ASP2151 Alone n=24 Participants ASP2151(1200 mg) alone	1200mg ASP2151 With Ritonavir n=24 Participants 1200mg ASP2151 alone followed by 1200mg ASP2151 + 600mg ritonavir ASP2151 ritonavir
Apparent Volume of Distribution (Vd/F) of ASP1955888-00	1840.8 L Standard Deviation 559.49	21474 L Standard Deviation 4135.72	2340.7 L Standard Deviation 877.14	27624.2 L Standard Deviation 14413.73

Adverse Events

400 mg ASP2151 Alone

Serious events: 0 serious events

Other events: 8 other events

Deaths: 0 deaths

400 mg ASP2151 With Ritonavir

Serious events: 0 serious events

Other events: 17 other events

Deaths: 0 deaths

1200 mg ASP2151 Alone

Serious events: 0 serious events

Other events: 15 other events

Deaths: 0 deaths

1200 mg ASP2151 With Ritonavir

Serious events: 0 serious events

Other events: 13 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	400 mg ASP2151 Alone n=24 participants at risk 400 mg ASP2151 alone	400 mg ASP2151 With Ritonavir n=24 participants at risk 400 mg ASP2151 with 600 mg ritonavir	1200 mg ASP2151 Alone n=24 participants at risk 1200 mg ASP2151 alone	1200 mg ASP2151 With Ritonavir n=24 participants at risk 1200 mg ASP2151 with 600 mg ritonavir
Nervous system disorders Headache	12.5% 3/24 • Up to 31 days after the final dose	25.0% 6/24 • Up to 31 days after the final dose	33.3% 8/24 • Up to 31 days after the final dose	29.2% 7/24 • Up to 31 days after the final dose
Nervous system disorders Dizziness	4.2% 1/24 • Up to 31 days after the final dose	8.3% 2/24 • Up to 31 days after the final dose	0.00% 0/24 • Up to 31 days after the final dose	4.2% 1/24 • Up to 31 days after the final dose
Nervous system disorders Migraine	0.00% 0/24 • Up to 31 days after the final dose	0.00% 0/24 • Up to 31 days after the final dose	0.00% 0/24 • Up to 31 days after the final dose	4.2% 1/24 • Up to 31 days after the final dose
Nervous system disorders Paraesthesia	0.00% 0/24 • Up to 31 days after the final dose	0.00% 0/24 • Up to 31 days after the final dose	4.2% 1/24 • Up to 31 days after the final dose	0.00% 0/24 • Up to 31 days after the final dose
Nervous system disorders Syncope	4.2% 1/24 • Up to 31 days after the final dose	0.00% 0/24 • Up to 31 days after the final dose	0.00% 0/24 • Up to 31 days after the final dose	0.00% 0/24 • Up to 31 days after the final dose
General disorders Fatigue	4.2% 1/24 • Up to 31 days after the final dose	16.7% 4/24 • Up to 31 days after the final dose	0.00% 0/24 • Up to 31 days after the final dose	0.00% 0/24 • Up to 31 days after the final dose
General disorders Catheter site related reaction	4.2% 1/24 • Up to 31 days after the final dose	4.2% 1/24 • Up to 31 days after the final dose	0.00% 0/24 • Up to 31 days after the final dose	4.2% 1/24 • Up to 31 days after the final dose
General disorders Asthenia	0.00% 0/24 • Up to 31 days after the final dose	0.00% 0/24 • Up to 31 days after the final dose	0.00% 0/24 • Up to 31 days after the final dose	4.2% 1/24 • Up to 31 days after the final dose
General disorders Catheter site pain	0.00% 0/24 • Up to 31 days after the final dose	0.00% 0/24 • Up to 31 days after the final dose	4.2% 1/24 • Up to 31 days after the final dose	0.00% 0/24 • Up to 31 days after the final dose
General disorders Feeling cold	4.2% 1/24 • Up to 31 days after the final dose	0.00% 0/24 • Up to 31 days after the final dose	0.00% 0/24 • Up to 31 days after the final dose	0.00% 0/24 • Up to 31 days after the final dose
General disorders Pyrexia	0.00% 0/24 • Up to 31 days after the final dose	0.00% 0/24 • Up to 31 days after the final dose	0.00% 0/24 • Up to 31 days after the final dose	4.2% 1/24 • Up to 31 days after the final dose
Infections and infestations Nasopharyngitis	4.2% 1/24 • Up to 31 days after the final dose	0.00% 0/24 • Up to 31 days after the final dose	4.2% 1/24 • Up to 31 days after the final dose	8.3% 2/24 • Up to 31 days after the final dose
Infections and infestations Rhinitis	0.00% 0/24 • Up to 31 days after the final dose	4.2% 1/24 • Up to 31 days after the final dose	12.5% 3/24 • Up to 31 days after the final dose	0.00% 0/24 • Up to 31 days after the final dose
Infections and infestations Upper respiratory tract infection	0.00% 0/24 • Up to 31 days after the final dose	4.2% 1/24 • Up to 31 days after the final dose	0.00% 0/24 • Up to 31 days after the final dose	0.00% 0/24 • Up to 31 days after the final dose
Gastrointestinal disorders Abdominal discomfort	0.00% 0/24 • Up to 31 days after the final dose	4.2% 1/24 • Up to 31 days after the final dose	0.00% 0/24 • Up to 31 days after the final dose	0.00% 0/24 • Up to 31 days after the final dose
Gastrointestinal disorders Cheilitis	0.00% 0/24 • Up to 31 days after the final dose	4.2% 1/24 • Up to 31 days after the final dose	0.00% 0/24 • Up to 31 days after the final dose	0.00% 0/24 • Up to 31 days after the final dose
Gastrointestinal disorders Diarrhoea	0.00% 0/24 • Up to 31 days after the final dose	0.00% 0/24 • Up to 31 days after the final dose	0.00% 0/24 • Up to 31 days after the final dose	4.2% 1/24 • Up to 31 days after the final dose
Gastrointestinal disorders Dyspepsia	0.00% 0/24 • Up to 31 days after the final dose	0.00% 0/24 • Up to 31 days after the final dose	4.2% 1/24 • Up to 31 days after the final dose	0.00% 0/24 • Up to 31 days after the final dose
Gastrointestinal disorders Sensitivity of teeth	0.00% 0/24 • Up to 31 days after the final dose	4.2% 1/24 • Up to 31 days after the final dose	0.00% 0/24 • Up to 31 days after the final dose	0.00% 0/24 • Up to 31 days after the final dose
Gastrointestinal disorders Toothache	0.00% 0/24 • Up to 31 days after the final dose	4.2% 1/24 • Up to 31 days after the final dose	0.00% 0/24 • Up to 31 days after the final dose	0.00% 0/24 • Up to 31 days after the final dose
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	8.3% 2/24 • Up to 31 days after the final dose	0.00% 0/24 • Up to 31 days after the final dose	0.00% 0/24 • Up to 31 days after the final dose	4.2% 1/24 • Up to 31 days after the final dose
Respiratory, thoracic and mediastinal disorders Epistaxis	0.00% 0/24 • Up to 31 days after the final dose	0.00% 0/24 • Up to 31 days after the final dose	4.2% 1/24 • Up to 31 days after the final dose	4.2% 1/24 • Up to 31 days after the final dose
Respiratory, thoracic and mediastinal disorders Cough	0.00% 0/24 • Up to 31 days after the final dose	4.2% 1/24 • Up to 31 days after the final dose	0.00% 0/24 • Up to 31 days after the final dose	0.00% 0/24 • Up to 31 days after the final dose
Musculoskeletal and connective tissue disorders Arthralgia	0.00% 0/24 • Up to 31 days after the final dose	0.00% 0/24 • Up to 31 days after the final dose	0.00% 0/24 • Up to 31 days after the final dose	4.2% 1/24 • Up to 31 days after the final dose
Musculoskeletal and connective tissue disorders Back pain	0.00% 0/24 • Up to 31 days after the final dose	0.00% 0/24 • Up to 31 days after the final dose	0.00% 0/24 • Up to 31 days after the final dose	4.2% 1/24 • Up to 31 days after the final dose
Musculoskeletal and connective tissue disorders joint swelling	0.00% 0/24 • Up to 31 days after the final dose	4.2% 1/24 • Up to 31 days after the final dose	0.00% 0/24 • Up to 31 days after the final dose	0.00% 0/24 • Up to 31 days after the final dose
Musculoskeletal and connective tissue disorders Myalgia	4.2% 1/24 • Up to 31 days after the final dose	0.00% 0/24 • Up to 31 days after the final dose	0.00% 0/24 • Up to 31 days after the final dose	0.00% 0/24 • Up to 31 days after the final dose
Skin and subcutaneous tissue disorders Hyperhidrosis	4.2% 1/24 • Up to 31 days after the final dose	0.00% 0/24 • Up to 31 days after the final dose	0.00% 0/24 • Up to 31 days after the final dose	0.00% 0/24 • Up to 31 days after the final dose
Skin and subcutaneous tissue disorders Pruritus generalised	4.2% 1/24 • Up to 31 days after the final dose	0.00% 0/24 • Up to 31 days after the final dose	0.00% 0/24 • Up to 31 days after the final dose	0.00% 0/24 • Up to 31 days after the final dose
Skin and subcutaneous tissue disorders Rash	0.00% 0/24 • Up to 31 days after the final dose	4.2% 1/24 • Up to 31 days after the final dose	0.00% 0/24 • Up to 31 days after the final dose	0.00% 0/24 • Up to 31 days after the final dose
Eye disorders Eye pruritus	0.00% 0/24 • Up to 31 days after the final dose	0.00% 0/24 • Up to 31 days after the final dose	4.2% 1/24 • Up to 31 days after the final dose	0.00% 0/24 • Up to 31 days after the final dose
Eye disorders Photophobia	0.00% 0/24 • Up to 31 days after the final dose	0.00% 0/24 • Up to 31 days after the final dose	0.00% 0/24 • Up to 31 days after the final dose	4.2% 1/24 • Up to 31 days after the final dose
Metabolism and nutrition disorders Decreased appetite	0.00% 0/24 • Up to 31 days after the final dose	4.2% 1/24 • Up to 31 days after the final dose	0.00% 0/24 • Up to 31 days after the final dose	0.00% 0/24 • Up to 31 days after the final dose

Additional Information

Maruho Co.,Ltd. Kyoto R&D Center

Clinical Development Dept.

Phone: +81-75-325-3255

Email: ctinfo@mii.maruho.co.jp

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place