Trial Outcomes & Findings for A Study to Determine the Antiviral Activity of TMC310911 When Administered With Ritonavir in Treatment-Naive Human Immunodeficiency Virus - Type 1 (HIV-1) Infected Patients (NCT NCT00838162)

Last Updated: 2013-06-12

Results Overview

The antiviral activity of TMC310911 is measured by the change in viral load from baseline in the 14 days of treatment following initiation of treatment with 4 different dosing regimens of TMC310911 coadministered with ritonavir.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

33 participants

Primary outcome timeframe

Baseline (Day 1), Day 8, Day 15

Results posted on

2013-06-12

Participant Flow

This study was conducted in Germany.

In total, 41 participants were screened of whom 33 participants were randomized and treated with TMC310911. All treated participants completed the study; there were no dropouts or discontinuations during the study.

Participant milestones

Participant milestones
Measure	TMC310911/Rtv 75/100 mg Twice Daily TMC310911 75 mg + ritonavir 100 mg twice daily on Days 1 to 14	TMC310911/Rtv 150/100 mg Twice Daily TMC310911 150 mg + ritonavir 100 mg twice daily on Days 1 to 14	TMC310911/Rtv 300/100 mg Twice Daily TMC310911 300 mg + ritonavir 100 mg twice daily on Days 1 to 14	TMC310911/Rtv 300/100 mg Once a Day TMC310911 300 mg + ritonavir 100 mg once a day on Days 1 to 14
Overall Study STARTED	9	8	8	8
Overall Study COMPLETED	9	8	8	8
Overall Study NOT COMPLETED	0	0	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

A Study to Determine the Antiviral Activity of TMC310911 When Administered With Ritonavir in Treatment-Naive Human Immunodeficiency Virus - Type 1 (HIV-1) Infected Patients

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	TMC310911/Rtv 75/100 mg Twice Daily n=9 Participants TMC310911 75 mg + ritonavir 100 mg twice daily on Days 1 to 14	TMC310911/Rtv 150/100 mg Twice Daily n=8 Participants TMC310911 150 mg + ritonavir 100 mg twice daily on Days 1 to 14	TMC310911/Rtv 300/100 mg Twice Daily n=8 Participants TMC310911 300 mg + ritonavir 100 mg twice daily on Days 1 to 14	TMC310911/Rtv 300/100 mg Once a Day n=8 Participants TMC310911 300 mg + ritonavir 100 mg once a day on Days 1 to 14	Total n=33 Participants Total of all reporting groups
Age Continuous	29.7 years STANDARD_DEVIATION 7.23 • n=5 Participants	38.1 years STANDARD_DEVIATION 8.66 • n=7 Participants	35.5 years STANDARD_DEVIATION 6.87 • n=5 Participants	37.8 years STANDARD_DEVIATION 10.19 • n=4 Participants	35.1 years STANDARD_DEVIATION 8.65 • n=21 Participants
Sex: Female, Male Female	1 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	1 Participants n=21 Participants
Sex: Female, Male Male	8 Participants n=5 Participants	8 Participants n=7 Participants	8 Participants n=5 Participants	8 Participants n=4 Participants	32 Participants n=21 Participants
Race/Ethnicity, Customized White	8 Participants n=5 Participants	8 Participants n=7 Participants	8 Participants n=5 Participants	8 Participants n=4 Participants	32 Participants n=21 Participants
Race/Ethnicity, Customized Black	1 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	1 Participants n=21 Participants

PRIMARY outcome

Timeframe: Baseline (Day 1), Day 8, Day 15

Population: Intent-to treat (ITT) population- participants who received at least 1 dose of study medication (TMC310911).

Outcome measures

Outcome measures
Measure	TMC310911/Rtv 75/100 mg Twice Daily n=9 Participants TMC310911 75 mg + ritonavir 100 mg twice daily on Days 1 to 14	TMC310911/Rtv 150/100 mg Twice Daily n=8 Participants TMC310911 150 mg + ritonavir 100 mg twice daily on Days 1 to 14	TMC310911/Rtv 300/100 mg Twice Daily n=8 Participants TMC310911 300 mg + ritonavir 100 mg twice daily on Days 1 to 14	TMC310911/Rtv 300/100 mg Once a Day n=8 Participants TMC310911 300 mg + ritonavir 100 mg once a day on Days 1 to 14
Mean Changes From Baseline in Plasma log10 Human Immunodeficiency Virus Type 1 Ribonucleic Acid (HIV-1 RNA) Baseline	4.72 log10 copies/mL Standard Error 0.245	4.36 log10 copies/mL Standard Error 0.259	4.78 log10 copies/mL Standard Error 0.161	4.71 log10 copies/mL Standard Error 0.116
Mean Changes From Baseline in Plasma log10 Human Immunodeficiency Virus Type 1 Ribonucleic Acid (HIV-1 RNA) Day 8	-1.30 log10 copies/mL Standard Error 0.126	-1.14 log10 copies/mL Standard Error 0.147	-1.07 log10 copies/mL Standard Error 0.104	-1.06 log10 copies/mL Standard Error 0.144
Mean Changes From Baseline in Plasma log10 Human Immunodeficiency Virus Type 1 Ribonucleic Acid (HIV-1 RNA) Day 15	-1.53 log10 copies/mL Standard Error 0.117	-1.79 log10 copies/mL Standard Error 0.192	-1.69 log10 copies/mL Standard Error 0.103	-1.55 log10 copies/mL Standard Error 0.160

SECONDARY outcome

Timeframe: 14 days

Population: Intent-to-treat (ITT) Population- all randomized participants who received at least 1 dose of study medication (TMC310911)

Virologic response is a viral load test result below a chosen threshold value (less than 50 copies/mL, less than 400 copies/mL, or at least 1 log drop in viral load) at any timepoint during a 14-day treatment of 4 different dose regimens of TMC310911 coadministered with 100 mg ritonavir.

Outcome measures

Outcome measures
Measure	TMC310911/Rtv 75/100 mg Twice Daily n=9 Participants TMC310911 75 mg + ritonavir 100 mg twice daily on Days 1 to 14	TMC310911/Rtv 150/100 mg Twice Daily n=8 Participants TMC310911 150 mg + ritonavir 100 mg twice daily on Days 1 to 14	TMC310911/Rtv 300/100 mg Twice Daily n=8 Participants TMC310911 300 mg + ritonavir 100 mg twice daily on Days 1 to 14	TMC310911/Rtv 300/100 mg Once a Day n=8 Participants TMC310911 300 mg + ritonavir 100 mg once a day on Days 1 to 14
Number of Participants With Virologic Response at Any Timepoint During the 14-day Treatment Period Viral load less than 50 copies/mL	0 Participants	1 Participants	0 Participants	0 Participants
Number of Participants With Virologic Response at Any Timepoint During the 14-day Treatment Period Viral load less than 400 copies/mL	3 Participants	4 Participants	1 Participants	0 Participants
Number of Participants With Virologic Response at Any Timepoint During the 14-day Treatment Period At least 1 log10 Viral Load Drop	9 Participants	8 Participants	8 Participants	7 Participants

SECONDARY outcome

Timeframe: Baseline (Day 1), Day 8, Day 15

Population: Intent-to-treat (ITT) Population - all randomized participants who received at least 1 dose of study medication (TMC310911)

Outcome measures

Outcome measures
Measure	TMC310911/Rtv 75/100 mg Twice Daily n=9 Participants TMC310911 75 mg + ritonavir 100 mg twice daily on Days 1 to 14	TMC310911/Rtv 150/100 mg Twice Daily n=8 Participants TMC310911 150 mg + ritonavir 100 mg twice daily on Days 1 to 14	TMC310911/Rtv 300/100 mg Twice Daily n=8 Participants TMC310911 300 mg + ritonavir 100 mg twice daily on Days 1 to 14	TMC310911/Rtv 300/100 mg Once a Day n=8 Participants TMC310911 300 mg + ritonavir 100 mg once a day on Days 1 to 14
Mean Changes From Baseline in CD4+ Cell Count Baseline	575.7 x 1000000 cells/L Standard Error 56.97	464.9 x 1000000 cells/L Standard Error 61.32	494.0 x 1000000 cells/L Standard Error 70.43	479.6 x 1000000 cells/L Standard Error 39.16
Mean Changes From Baseline in CD4+ Cell Count Day 8	-21.0 x 1000000 cells/L Standard Error 41.23	40.3 x 1000000 cells/L Standard Error 45.19	-14.8 x 1000000 cells/L Standard Error 47.59	17.9 x 1000000 cells/L Standard Error 48.20
Mean Changes From Baseline in CD4+ Cell Count Day 15	-33.7 x 1000000 cells/L Standard Error 27.04	-2.8 x 1000000 cells/L Standard Error 31.44	-2.0 x 1000000 cells/L Standard Error 41.23	92.5 x 1000000 cells/L Standard Error 58.70

SECONDARY outcome

Timeframe: Day 1 and Day 14

Population: Intent-to-treat (ITT) population - all randomized participants who received at least 1 dose of study medication (TMC310911)

Outcome measures

Outcome measures
Measure	TMC310911/Rtv 75/100 mg Twice Daily n=9 Participants TMC310911 75 mg + ritonavir 100 mg twice daily on Days 1 to 14	TMC310911/Rtv 150/100 mg Twice Daily n=8 Participants TMC310911 150 mg + ritonavir 100 mg twice daily on Days 1 to 14	TMC310911/Rtv 300/100 mg Twice Daily n=8 Participants TMC310911 300 mg + ritonavir 100 mg twice daily on Days 1 to 14	TMC310911/Rtv 300/100 mg Once a Day n=8 Participants TMC310911 300 mg + ritonavir 100 mg once a day on Days 1 to 14
Maximum Plasma Concentration (Cmax) of TMC310911 Day 1	487.9 ng/mL Standard Deviation 450.3	623.0 ng/mL Standard Deviation 358.1	706.3 ng/mL Standard Deviation 553.2	1924 ng/mL Standard Deviation 1048
Maximum Plasma Concentration (Cmax) of TMC310911 Day 14	589.7 ng/mL Standard Deviation 554.1	1674 ng/mL Standard Deviation 652.3	2256 ng/mL Standard Deviation 961.9	2963 ng/mL Standard Deviation 1920

SECONDARY outcome

Timeframe: Day 1 and Day 14

Population: Intent-to-treat (ITT) population - all randomized participants who received at least 1 dose of study medication (TMC310911)

Outcome measures

Outcome measures
Measure	TMC310911/Rtv 75/100 mg Twice Daily n=9 Participants TMC310911 75 mg + ritonavir 100 mg twice daily on Days 1 to 14	TMC310911/Rtv 150/100 mg Twice Daily n=8 Participants TMC310911 150 mg + ritonavir 100 mg twice daily on Days 1 to 14	TMC310911/Rtv 300/100 mg Twice Daily n=8 Participants TMC310911 300 mg + ritonavir 100 mg twice daily on Days 1 to 14	TMC310911/Rtv 300/100 mg Once a Day n=8 Participants TMC310911 300 mg + ritonavir 100 mg once a day on Days 1 to 14
Time to Reach the Maximum Plasma Concentration (Tmax) of TMC310911 Day 1	5.02 hours Interval 2.0 to 12.0	5.00 hours Interval 3.0 to 8.12	5.06 hours Interval 5.0 to 12.17	5.00 hours Interval 2.0 to 5.02
Time to Reach the Maximum Plasma Concentration (Tmax) of TMC310911 Day 14	4.98 hours Interval 1.0 to 8.0	3.00 hours Interval 1.0 to 5.03	3.87 hours Interval 0.0 to 5.02	3.02 hours Interval 1.02 to 5.03

SECONDARY outcome

Timeframe: Day 1 and Day 14

Population: Intent-to-treat (ITT) population - all randomized participants who received at least 1 dose of study medication (TMC310911)

Outcome measures

Outcome measures
Measure	TMC310911/Rtv 75/100 mg Twice Daily n=8 Participants TMC310911 75 mg + ritonavir 100 mg twice daily on Days 1 to 14	TMC310911/Rtv 150/100 mg Twice Daily n=8 Participants TMC310911 150 mg + ritonavir 100 mg twice daily on Days 1 to 14	TMC310911/Rtv 300/100 mg Twice Daily n=7 Participants TMC310911 300 mg + ritonavir 100 mg twice daily on Days 1 to 14	TMC310911/Rtv 300/100 mg Once a Day n=7 Participants TMC310911 300 mg + ritonavir 100 mg once a day on Days 1 to 14
Area Under the Plasma Concentration-time Curve (AUC12) From the Time of Administration of TMC310911 up to 12 Hours After Dosing Day 1	2519 ng.h/mL Standard Deviation 2123	2735 ng.h/mL Standard Deviation 1572	2990 ng.h/mL Standard Deviation 2245	10040 ng.h/mL Standard Deviation 6122
Area Under the Plasma Concentration-time Curve (AUC12) From the Time of Administration of TMC310911 up to 12 Hours After Dosing Day 14	4031 ng.h/mL Standard Deviation 3845	10680 ng.h/mL Standard Deviation 3147	16010 ng.h/mL Standard Deviation 8229	17520 ng.h/mL Standard Deviation 11610

SECONDARY outcome

Timeframe: Day 2, Day 3, Day 4, Day 6, Day 8, Day 10, Day 12 and Day 14

Population: Intent-to-treat (ITT) population - all randomized participants who received at least 1 dose of study medication (TMC310911).

Outcome measures

Outcome measures
Measure	TMC310911/Rtv 75/100 mg Twice Daily n=9 Participants TMC310911 75 mg + ritonavir 100 mg twice daily on Days 1 to 14	TMC310911/Rtv 150/100 mg Twice Daily n=8 Participants TMC310911 150 mg + ritonavir 100 mg twice daily on Days 1 to 14	TMC310911/Rtv 300/100 mg Twice Daily n=8 Participants TMC310911 300 mg + ritonavir 100 mg twice daily on Days 1 to 14	TMC310911/Rtv 300/100 mg Once a Day n=8 Participants TMC310911 300 mg + ritonavir 100 mg once a day on Days 1 to 14
Predose Plasma Concentration (C0h) of TMC310911 Day 10	78.51 ng/mL Standard Deviation 57.88	394.4 ng/mL Standard Deviation 134.4	736.1 ng/mL Standard Deviation 435.0	251.7 ng/mL Standard Deviation 211.0
Predose Plasma Concentration (C0h) of TMC310911 Day 2	79.95 ng/mL Standard Deviation 104.1	207.7 ng/mL Standard Deviation 122.9	231.9 ng/mL Standard Deviation 199.9	45.48 ng/mL Standard Deviation 28.94
Predose Plasma Concentration (C0h) of TMC310911 Day 3	93.98 ng/mL Standard Deviation 92.90	448.0 ng/mL Standard Deviation 266.1	586.3 ng/mL Standard Deviation 454.2	125.9 ng/mL Standard Deviation 69.01
Predose Plasma Concentration (C0h) of TMC310911 Day 4	88.94 ng/mL Standard Deviation 113.6	291.3 ng/mL Standard Deviation 170.2	1035 ng/mL Standard Deviation 552.2	191.0 ng/mL Standard Deviation 175.7
Predose Plasma Concentration (C0h) of TMC310911 Day 6	119.1 ng/mL Standard Deviation 182.1	443.0 ng/mL Standard Deviation 284.7	960.5 ng/mL Standard Deviation 506.9	250.0 ng/mL Standard Deviation 236.1
Predose Plasma Concentration (C0h) of TMC310911 Day 8	134.5 ng/mL Standard Deviation 179.0	665.9 ng/mL Standard Deviation 461.1	1028 ng/mL Standard Deviation 724.1	239.6 ng/mL Standard Deviation 242.6
Predose Plasma Concentration (C0h) of TMC310911 Day 12	104.6 ng/mL Standard Deviation 82.91	518.6 ng/mL Standard Deviation 288.7	1110 ng/mL Standard Deviation 547.5	250.2 ng/mL Standard Deviation 181.9
Predose Plasma Concentration (C0h) of TMC310911 Day 14	152.5 ng/mL Standard Deviation 248.2	420.9 ng/mL Standard Deviation 244.6	924.8 ng/mL Standard Deviation 527.9	209.9 ng/mL Standard Deviation 187.2

SECONDARY outcome

Timeframe: Day 14

Population: Intent-to-treat (ITT) population - all randomized participants who received at least 1 dose of study medication (TMC310911).

Outcome measures

Outcome measures
Measure	TMC310911/Rtv 75/100 mg Twice Daily n=8 Participants TMC310911 75 mg + ritonavir 100 mg twice daily on Days 1 to 14	TMC310911/Rtv 150/100 mg Twice Daily n=7 Participants TMC310911 150 mg + ritonavir 100 mg twice daily on Days 1 to 14	TMC310911/Rtv 300/100 mg Twice Daily n=7 Participants TMC310911 300 mg + ritonavir 100 mg twice daily on Days 1 to 14	TMC310911/Rtv 300/100 mg Once a Day n=8 Participants TMC310911 300 mg + ritonavir 100 mg once a day on Days 1 to 14
Average Steady-state Plasma Concentration (Css,av) of TMC310911	336.2 ng/mL Standard Deviation 321.3	889.6 ng/mL Standard Deviation 262.6	1340 ng/mL Standard Deviation 689.6	887.3 ng/mL Standard Deviation 567.5

SECONDARY outcome

Timeframe: Day 14

Population: Intent-to-treat (ITT) population - all randomized participants who received at least 1 dose of study medication (TMC310911)

Fluctuation index, ie, percentage fluctuation: variation between maximum (Cmax) and minimum (Cmin) plasma concentration at steady-state, calculated as: 100 x (\[Cmax-Cmin\]/Css,av). Css,av is an average steady-state plasma concentration.

Outcome measures

Outcome measures
Measure	TMC310911/Rtv 75/100 mg Twice Daily n=8 Participants TMC310911 75 mg + ritonavir 100 mg twice daily on Days 1 to 14	TMC310911/Rtv 150/100 mg Twice Daily n=7 Participants TMC310911 150 mg + ritonavir 100 mg twice daily on Days 1 to 14	TMC310911/Rtv 300/100 mg Twice Daily n=7 Participants TMC310911 300 mg + ritonavir 100 mg twice daily on Days 1 to 14	TMC310911/Rtv 300/100 mg Once a Day n=8 Participants TMC310911 300 mg + ritonavir 100 mg once a day on Days 1 to 14
Fluctuation Index of TMC310911	181.0 Percent ng/mL Standard Deviation 80.00	161.3 Percent ng/mL Standard Deviation 29.22	129.2 Percent ng/mL Standard Deviation 52.89	331.8 Percent ng/mL Standard Deviation 55.47

Adverse Events

TMC310911/Rtv 75/100 mg Twice Daily

Serious events: 0 serious events

Other events: 5 other events

Deaths: 0 deaths

TMC310911/Rtv 150/100 mg Twice Daily

Serious events: 0 serious events

Other events: 5 other events

Deaths: 0 deaths

TMC310911/Rtv 300/100 mg Twice Daily

Serious events: 0 serious events

Other events: 6 other events

Deaths: 0 deaths

TMC310911/Rtv 300/100 mg Once a Day

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Additional Information

VP Head of Discovery & Early Development

Jan-Cil UK

Phone: 44 1494 553458

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: GT60

Measure	TMC310911/Rtv 75/100 mg Twice Daily n=9 participants at risk TMC310911 75 mg + ritonavir 100 mg twice daily on Days 1 to 14	TMC310911/Rtv 150/100 mg Twice Daily n=8 participants at risk TMC310911 150 mg + ritonavir 100 mg twice daily on Days 1 to 14	TMC310911/Rtv 300/100 mg Twice Daily n=8 participants at risk TMC310911 300 mg + ritonavir 100 mg twice daily on Days 1 to 14	TMC310911/Rtv 300/100 mg Once a Day n=8 participants at risk TMC310911 300 mg + ritonavir 100 mg once a day on Days 1 to 14
Eye disorders Conjunctivitis	0.00% 0/9 • Up to 4 weeks after the last dose administration of study medication	0.00% 0/8 • Up to 4 weeks after the last dose administration of study medication	12.5% 1/8 • Up to 4 weeks after the last dose administration of study medication	0.00% 0/8 • Up to 4 weeks after the last dose administration of study medication
Gastrointestinal disorders Abdominal pain upper	11.1% 1/9 • Up to 4 weeks after the last dose administration of study medication	0.00% 0/8 • Up to 4 weeks after the last dose administration of study medication	0.00% 0/8 • Up to 4 weeks after the last dose administration of study medication	0.00% 0/8 • Up to 4 weeks after the last dose administration of study medication
Gastrointestinal disorders Abnormal faeces	11.1% 1/9 • Up to 4 weeks after the last dose administration of study medication	0.00% 0/8 • Up to 4 weeks after the last dose administration of study medication	0.00% 0/8 • Up to 4 weeks after the last dose administration of study medication	0.00% 0/8 • Up to 4 weeks after the last dose administration of study medication
Gastrointestinal disorders Diarrhoea	11.1% 1/9 • Up to 4 weeks after the last dose administration of study medication	12.5% 1/8 • Up to 4 weeks after the last dose administration of study medication	12.5% 1/8 • Up to 4 weeks after the last dose administration of study medication	0.00% 0/8 • Up to 4 weeks after the last dose administration of study medication
Gastrointestinal disorders Dry mouth	0.00% 0/9 • Up to 4 weeks after the last dose administration of study medication	0.00% 0/8 • Up to 4 weeks after the last dose administration of study medication	12.5% 1/8 • Up to 4 weeks after the last dose administration of study medication	0.00% 0/8 • Up to 4 weeks after the last dose administration of study medication
Gastrointestinal disorders Eructation	0.00% 0/9 • Up to 4 weeks after the last dose administration of study medication	0.00% 0/8 • Up to 4 weeks after the last dose administration of study medication	0.00% 0/8 • Up to 4 weeks after the last dose administration of study medication	12.5% 1/8 • Up to 4 weeks after the last dose administration of study medication
Gastrointestinal disorders Flatulence	11.1% 1/9 • Up to 4 weeks after the last dose administration of study medication	0.00% 0/8 • Up to 4 weeks after the last dose administration of study medication	0.00% 0/8 • Up to 4 weeks after the last dose administration of study medication	0.00% 0/8 • Up to 4 weeks after the last dose administration of study medication
Gastrointestinal disorders Frequent bowel movements	0.00% 0/9 • Up to 4 weeks after the last dose administration of study medication	12.5% 1/8 • Up to 4 weeks after the last dose administration of study medication	12.5% 1/8 • Up to 4 weeks after the last dose administration of study medication	0.00% 0/8 • Up to 4 weeks after the last dose administration of study medication
Gastrointestinal disorders Nausea	11.1% 1/9 • Up to 4 weeks after the last dose administration of study medication	37.5% 3/8 • Up to 4 weeks after the last dose administration of study medication	0.00% 0/8 • Up to 4 weeks after the last dose administration of study medication	0.00% 0/8 • Up to 4 weeks after the last dose administration of study medication
Gastrointestinal disorders Toothache	0.00% 0/9 • Up to 4 weeks after the last dose administration of study medication	0.00% 0/8 • Up to 4 weeks after the last dose administration of study medication	12.5% 1/8 • Up to 4 weeks after the last dose administration of study medication	0.00% 0/8 • Up to 4 weeks after the last dose administration of study medication
Gastrointestinal disorders Vomiting	0.00% 0/9 • Up to 4 weeks after the last dose administration of study medication	12.5% 1/8 • Up to 4 weeks after the last dose administration of study medication	0.00% 0/8 • Up to 4 weeks after the last dose administration of study medication	0.00% 0/8 • Up to 4 weeks after the last dose administration of study medication
General disorders Discomfort	0.00% 0/9 • Up to 4 weeks after the last dose administration of study medication	0.00% 0/8 • Up to 4 weeks after the last dose administration of study medication	0.00% 0/8 • Up to 4 weeks after the last dose administration of study medication	12.5% 1/8 • Up to 4 weeks after the last dose administration of study medication
General disorders Fatigue	33.3% 3/9 • Up to 4 weeks after the last dose administration of study medication	25.0% 2/8 • Up to 4 weeks after the last dose administration of study medication	50.0% 4/8 • Up to 4 weeks after the last dose administration of study medication	0.00% 0/8 • Up to 4 weeks after the last dose administration of study medication
General disorders Influenza like illness	11.1% 1/9 • Up to 4 weeks after the last dose administration of study medication	0.00% 0/8 • Up to 4 weeks after the last dose administration of study medication	0.00% 0/8 • Up to 4 weeks after the last dose administration of study medication	0.00% 0/8 • Up to 4 weeks after the last dose administration of study medication
Infections and infestations Cytomegalovirus hepatitis	0.00% 0/9 • Up to 4 weeks after the last dose administration of study medication	0.00% 0/8 • Up to 4 weeks after the last dose administration of study medication	0.00% 0/8 • Up to 4 weeks after the last dose administration of study medication	12.5% 1/8 • Up to 4 weeks after the last dose administration of study medication
Infections and infestations Folliculitis	0.00% 0/9 • Up to 4 weeks after the last dose administration of study medication	12.5% 1/8 • Up to 4 weeks after the last dose administration of study medication	0.00% 0/8 • Up to 4 weeks after the last dose administration of study medication	0.00% 0/8 • Up to 4 weeks after the last dose administration of study medication
Infections and infestations Genital herpes	0.00% 0/9 • Up to 4 weeks after the last dose administration of study medication	0.00% 0/8 • Up to 4 weeks after the last dose administration of study medication	12.5% 1/8 • Up to 4 weeks after the last dose administration of study medication	0.00% 0/8 • Up to 4 weeks after the last dose administration of study medication
Infections and infestations Nasopharyngitis	11.1% 1/9 • Up to 4 weeks after the last dose administration of study medication	0.00% 0/8 • Up to 4 weeks after the last dose administration of study medication	0.00% 0/8 • Up to 4 weeks after the last dose administration of study medication	12.5% 1/8 • Up to 4 weeks after the last dose administration of study medication
Infections and infestations Respiratory tract infection	0.00% 0/9 • Up to 4 weeks after the last dose administration of study medication	12.5% 1/8 • Up to 4 weeks after the last dose administration of study medication	0.00% 0/8 • Up to 4 weeks after the last dose administration of study medication	0.00% 0/8 • Up to 4 weeks after the last dose administration of study medication
Injury, poisoning and procedural complications Skeletal injury	0.00% 0/9 • Up to 4 weeks after the last dose administration of study medication	0.00% 0/8 • Up to 4 weeks after the last dose administration of study medication	12.5% 1/8 • Up to 4 weeks after the last dose administration of study medication	0.00% 0/8 • Up to 4 weeks after the last dose administration of study medication
Investigations Alanine aminotransferase increased	0.00% 0/9 • Up to 4 weeks after the last dose administration of study medication	12.5% 1/8 • Up to 4 weeks after the last dose administration of study medication	0.00% 0/8 • Up to 4 weeks after the last dose administration of study medication	0.00% 0/8 • Up to 4 weeks after the last dose administration of study medication
Investigations Aspartate aminotransferase increased	0.00% 0/9 • Up to 4 weeks after the last dose administration of study medication	12.5% 1/8 • Up to 4 weeks after the last dose administration of study medication	0.00% 0/8 • Up to 4 weeks after the last dose administration of study medication	0.00% 0/8 • Up to 4 weeks after the last dose administration of study medication
Musculoskeletal and connective tissue disorders Muscle spasms	0.00% 0/9 • Up to 4 weeks after the last dose administration of study medication	0.00% 0/8 • Up to 4 weeks after the last dose administration of study medication	0.00% 0/8 • Up to 4 weeks after the last dose administration of study medication	12.5% 1/8 • Up to 4 weeks after the last dose administration of study medication
Nervous system disorders Dizziness	0.00% 0/9 • Up to 4 weeks after the last dose administration of study medication	0.00% 0/8 • Up to 4 weeks after the last dose administration of study medication	12.5% 1/8 • Up to 4 weeks after the last dose administration of study medication	0.00% 0/8 • Up to 4 weeks after the last dose administration of study medication
Nervous system disorders Headache	0.00% 0/9 • Up to 4 weeks after the last dose administration of study medication	12.5% 1/8 • Up to 4 weeks after the last dose administration of study medication	0.00% 0/8 • Up to 4 weeks after the last dose administration of study medication	12.5% 1/8 • Up to 4 weeks after the last dose administration of study medication
Renal and urinary disorders Micturition urgency	22.2% 2/9 • Up to 4 weeks after the last dose administration of study medication	0.00% 0/8 • Up to 4 weeks after the last dose administration of study medication	0.00% 0/8 • Up to 4 weeks after the last dose administration of study medication	0.00% 0/8 • Up to 4 weeks after the last dose administration of study medication
Skin and subcutaneous tissue disorders Night sweats	0.00% 0/9 • Up to 4 weeks after the last dose administration of study medication	0.00% 0/8 • Up to 4 weeks after the last dose administration of study medication	0.00% 0/8 • Up to 4 weeks after the last dose administration of study medication	12.5% 1/8 • Up to 4 weeks after the last dose administration of study medication
Skin and subcutaneous tissue disorders Skin discolouration	0.00% 0/9 • Up to 4 weeks after the last dose administration of study medication	12.5% 1/8 • Up to 4 weeks after the last dose administration of study medication	0.00% 0/8 • Up to 4 weeks after the last dose administration of study medication	0.00% 0/8 • Up to 4 weeks after the last dose administration of study medication