Trial Outcomes & Findings for A Study of LY2510924 and Durvalumab in Participants With Solid Tumors (NCT NCT02737072)

Last Updated: 2019-08-12

Results Overview

DLT is defined as 1 of the following adverse events(AE) reported during the Phase 1a DLT observation period,if considered to be definitely,probably,or possibly related to either study regimen by the investigator;and fulfills any 1 of the following criterion using(NCI)CTCAE version(v)4.03:Grade4 immune-related AE,Grade4 non-laboratory AE,any CTCAE Grade ≥3 QT prolongation AE,≥Grade3 colitis or noninfectious pneumonitis irrespective of duration,Grade3 immune-related AE(excluding colitis,QT prolongation,or pneumonitis) that does not downgrade to Grade2 within 3 days after onset of event despite optimal medical management including systemic corticosteroids,or does not downgrade to ≤Grade 1 or baseline within 14 days,Grade2 pneumonitis that does not resolve to ≤Grade 1 within 3 days of the initiation of maximal supportive care,including corticosteroid therapy,Grade3 toxicity lasting an extended time despite optimal supportive care and there were also laboratory abnormalities criterion.

Recruitment status

TERMINATED

Study phase

PHASE1

Target enrollment

9 participants

Primary outcome timeframe

Cycle 1 (28 Days)

Results posted on

2019-08-12

Participant Flow

This study was conducted in 2 parts. Phase 1a of the study consisted of a dose-escalation assessment and Phase 1b of the study included 2 expansion arms. The study was terminated after the Phase 1a part was complete. A participant completed the study if they completed at least 1 cycle.

Participant milestones

Participant milestones
Measure	20 mg LY2510924 + 1500 mg Durvalumab 20 milligrams (mg) LY2510924 given subcutaneously (SQ) once daily in combination with 1500 mg durvalumab given intravenously (IV) on Day 1 of each cycle (28 days).	30 mg LY2510924 + 1500 mg Durvalumab 30 mg LY2510924 given SQ once daily in combination with 1500 mg durvalumab given IV on Day 1 of each cycle (28 days).	40 mg LY2510924 + 1500 mg Durvalumab 40 mg LY2510924 given SQ once daily in combination with 1500 mg durvalumab given IV on Day 1 of each cycle (28 days).
Overall Study STARTED	3	3	3
Overall Study Received at Least One Dose of Drug	3	3	3
Overall Study COMPLETED	3	3	3
Overall Study NOT COMPLETED	0	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

A Study of LY2510924 and Durvalumab in Participants With Solid Tumors

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	20 mg LY2510924 + 1500 mg Durvalumab n=3 Participants 20 milligrams (mg) LY2510924 given subcutaneously (SQ) once daily in combination with 1500 mg durvalumab given intravenously (IV) on Day 1 of each cycle (28 days).	30 mg LY2510924 + 1500 mg Durvalumab n=3 Participants 30 mg LY2510924 given SQ once daily in combination with 1500 mg durvalumab given IV on Day 1 of each cycle (28 days).	40 mg LY2510924 + 1500 mg Durvalumab n=3 Participants 40 mg LY2510924 given SQ once daily in combination with 1500 mg durvalumab given IV on Day 1 of each cycle (28 days).	Total n=9 Participants Total of all reporting groups
Age, Continuous	56.33 years STANDARD_DEVIATION 22.12 • n=5 Participants	60.00 years STANDARD_DEVIATION 7.55 • n=7 Participants	48.33 years STANDARD_DEVIATION 3.21 • n=5 Participants	54.89 years STANDARD_DEVIATION 12.88 • n=4 Participants
Sex: Female, Male Female	1 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants	3 Participants n=4 Participants
Sex: Female, Male Male	2 Participants n=5 Participants	3 Participants n=7 Participants	1 Participants n=5 Participants	6 Participants n=4 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	3 Participants n=5 Participants	3 Participants n=7 Participants	3 Participants n=5 Participants	9 Participants n=4 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 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	0 Participants n=4 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) White	3 Participants n=5 Participants	3 Participants n=7 Participants	3 Participants n=5 Participants	9 Participants n=4 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Region of Enrollment United States	3 Participants n=5 Participants	3 Participants n=7 Participants	3 Participants n=5 Participants	9 Participants n=4 Participants

PRIMARY outcome

Timeframe: Cycle 1 (28 Days)

Population: All participants who received at least one of dose of study drug.

Outcome measures

Outcome measures
Measure	20 mg LY2510924 + 1500 mg Durvalumab n=3 Participants 20 milligrams (mg) LY2510924 given subcutaneously (SQ) once daily in combination with 1500 mg durvalumab given intravenously (IV) on Day 1 of each cycle (28 days).	30 mg LY2510924 + 1500 mg Durvalumab n=3 Participants 30 mg LY2510924 given SQ once daily in combination with 1500 mg durvalumab given IV on Day 1 of each cycle (28 days).	40 mg LY2510924 + 1500 mg Durvalumab n=3 Participants 40 mg LY2510924 given SQ once daily in combination with 1500 mg durvalumab given IV on Day 1 of each cycle (28 days).
Number of Participants Who Experienced Dose-Limiting Toxicities (DLTs)	0 Participants	0 Participants	0 Participants

PRIMARY outcome

Timeframe: Cycle 1 (28 Days)

Population: All phase 1a participants who received at least one dose of study drug.

MTD was determined after the evaluation of Phase 1a portion of the trial. For Phase 1a, any DLT-equivalent toxicities observed in Cycle 2 and beyond were also be considered in dose escalation and determining MTD/recommended Phase 2 dose. See outcome measure number 1 for the DLT criterion.

Outcome measures

Outcome measures
Measure	20 mg LY2510924 + 1500 mg Durvalumab n=3 Participants 20 milligrams (mg) LY2510924 given subcutaneously (SQ) once daily in combination with 1500 mg durvalumab given intravenously (IV) on Day 1 of each cycle (28 days).	30 mg LY2510924 + 1500 mg Durvalumab 30 mg LY2510924 given SQ once daily in combination with 1500 mg durvalumab given IV on Day 1 of each cycle (28 days).	40 mg LY2510924 + 1500 mg Durvalumab 40 mg LY2510924 given SQ once daily in combination with 1500 mg durvalumab given IV on Day 1 of each cycle (28 days).
Maximum Tolerated Dose (MTD) of LY2510924	40 milligram (mg)	—	—

SECONDARY outcome

Timeframe: Cycle 1 Day 1: Predose, 0.5, 2, 4, 6, 8, 24-30 hours; Day 15: Predose, 0.5, 2, 4, 6, 8 hours

Population: All participants who received at least one dose of study drug.

Pharmacokinetics: Area Under the Concentration-Time Curve (AUC \[0-∞\]) of LY2510924 when Co-Administered with Durvalumab

Outcome measures

Outcome measures
Measure	20 mg LY2510924 + 1500 mg Durvalumab n=3 Participants 20 milligrams (mg) LY2510924 given subcutaneously (SQ) once daily in combination with 1500 mg durvalumab given intravenously (IV) on Day 1 of each cycle (28 days).	30 mg LY2510924 + 1500 mg Durvalumab n=3 Participants 30 mg LY2510924 given SQ once daily in combination with 1500 mg durvalumab given IV on Day 1 of each cycle (28 days).	40 mg LY2510924 + 1500 mg Durvalumab n=3 Participants 40 mg LY2510924 given SQ once daily in combination with 1500 mg durvalumab given IV on Day 1 of each cycle (28 days).
Pharmacokinetics: Area Under the Concentration-Time Curve (AUC [0-∞]) of LY2510924 When Co-Administered With Durvalumab Day 1	3390 nanogramhour /milliliter (ng h/mL) Geometric Coefficient of Variation 33	3430 nanogramhour /milliliter (ng h/mL) Geometric Coefficient of Variation 17	7490 nanogramhour /milliliter (ng h/mL) Geometric Coefficient of Variation 57
Pharmacokinetics: Area Under the Concentration-Time Curve (AUC [0-∞]) of LY2510924 When Co-Administered With Durvalumab Day 15	1960 nanogramhour /milliliter (ng h/mL) Geometric Coefficient of Variation 258	4320 nanogramhour /milliliter (ng h/mL) Geometric Coefficient of Variation 11	NA nanogramhour /milliliter (ng h/mL) Geometric Coefficient of Variation NA For n=2, only range 6210 - 170000 was calculated.

SECONDARY outcome

Timeframe: Predose Cycle 1 Day 1 through 90 Day Post Treatment Follow Up (Up To 12 Months)

Population: All participants who received at least one dose of study drug.

Number of participants with treatment-emergent positive Anti-Durvalumab antibodies was summarized by treatment group.

Outcome measures

Outcome measures
Measure	20 mg LY2510924 + 1500 mg Durvalumab n=3 Participants 20 milligrams (mg) LY2510924 given subcutaneously (SQ) once daily in combination with 1500 mg durvalumab given intravenously (IV) on Day 1 of each cycle (28 days).	30 mg LY2510924 + 1500 mg Durvalumab n=3 Participants 30 mg LY2510924 given SQ once daily in combination with 1500 mg durvalumab given IV on Day 1 of each cycle (28 days).	40 mg LY2510924 + 1500 mg Durvalumab n=3 Participants 40 mg LY2510924 given SQ once daily in combination with 1500 mg durvalumab given IV on Day 1 of each cycle (28 days).
Number of Participants With Anti-Durvalumab Antibodies When Administered in Combination With LY2510924	0 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Baseline through Measured Progressive Disease or Death (Up To 12 Months)

Population: All participants who received at least one dose of study drug.

Best overall response of CR or PR was defined using RECIST v 1.1 criteria. CR was defined as the disappearance of all lesions, pathological lymph node reduction in short axis to \<10 mm, and normalization of tumor marker levels of non-target lesions. PR was defined as ≥30% decrease in sum of diameter(SOD) of target lesions taking as reference the baseline sum diameter. PD was defined as ≥20% increase in SOD of target lesions and short axes of target lymph nodes, taking as reference the smallest sum of the longest diameters recorded since treatment started and an absolute increase in sum diameter of ≥5 mm; appearance of ≥1 new lesions and/or unequivocal progression of existing non-target lesions. Participants who had no post baseline tumor assessments were considered non-responders and included in the denominator when calculating response rate. Percentage of participants=(number of participants with CR+PR/total number of participants)\*100.

Outcome measures

Outcome measures
Measure	20 mg LY2510924 + 1500 mg Durvalumab n=3 Participants 20 milligrams (mg) LY2510924 given subcutaneously (SQ) once daily in combination with 1500 mg durvalumab given intravenously (IV) on Day 1 of each cycle (28 days).	30 mg LY2510924 + 1500 mg Durvalumab n=3 Participants 30 mg LY2510924 given SQ once daily in combination with 1500 mg durvalumab given IV on Day 1 of each cycle (28 days).	40 mg LY2510924 + 1500 mg Durvalumab n=3 Participants 40 mg LY2510924 given SQ once daily in combination with 1500 mg durvalumab given IV on Day 1 of each cycle (28 days).
Percentage of Participants With Best Overall Response of Complete Response (CR) or Partial Response (PR) [Objective Response Rate (ORR)]	0 percentage of participants	0 percentage of participants	0 percentage of participants

SECONDARY outcome

Timeframe: Baseline through Measured Progressive Disease (Up To 12 Months)

Population: All participants who received at least one dose of study drug.

DCR: percentage of participants with CR, PR, or SD using RECIST v 1.1 criteria. CR: disappearance of all lesions, pathological lymph node reduction in short axis to \<10 mm, and normalization of tumor marker levels of non-target lesions. PR: ≥30% decrease in sum of diameter (SOD) of target lesions taking as reference baseline sum diameter. PD: ≥20% increase in SOD of target lesions and short axes of target lymph nodes, taking as reference smallest sum of longest diameters recorded since treatment started and an absolute increase in sum diameter ≥5 mm; appearance of ≥1 new lesions and/or unequivocal progression of existing non-target lesions. SD: neither sufficient shrinkage to qualify for PR nor increase to qualify for PD. Participants who had no post baseline tumor assessments were considered non-responders and included in the denominator when calculating response rate. Percentage of participants=(number of participants with CR+PR+SD/total number of participants)\*100.

Outcome measures

Outcome measures
Measure	20 mg LY2510924 + 1500 mg Durvalumab n=3 Participants 20 milligrams (mg) LY2510924 given subcutaneously (SQ) once daily in combination with 1500 mg durvalumab given intravenously (IV) on Day 1 of each cycle (28 days).	30 mg LY2510924 + 1500 mg Durvalumab n=3 Participants 30 mg LY2510924 given SQ once daily in combination with 1500 mg durvalumab given IV on Day 1 of each cycle (28 days).	40 mg LY2510924 + 1500 mg Durvalumab n=3 Participants 40 mg LY2510924 given SQ once daily in combination with 1500 mg durvalumab given IV on Day 1 of each cycle (28 days).
Percentage of Participants With CR, PR, or Stable Disease (SD) (Disease Control Rate [DCR])	100 percentage of participants	33.3 percentage of participants	0 percentage of participants

Adverse Events

20 mg LY2510924 + 1500 mg Durvalumab

Serious events: 0 serious events

Other events: 3 other events

Deaths: 2 deaths

30 mg LY2510924 + 1500 mg Durvalumab

Serious events: 1 serious events

Other events: 3 other events

Deaths: 3 deaths

40 mg LY2510924 + 1500 mg Durvalumab

Serious events: 1 serious events

Other events: 3 other events

Deaths: 1 deaths

Serious adverse events

Serious adverse events
Measure	20 mg LY2510924 + 1500 mg Durvalumab n=3 participants at risk 20 milligrams (mg) LY2510924 given subcutaneously (SQ) once daily in combination with 1500 mg durvalumab given intravenously (IV) on Day 1 of each cycle (28 days).	30 mg LY2510924 + 1500 mg Durvalumab n=3 participants at risk 30 mg LY2510924 given SQ once daily in combination with 1500 mg durvalumab given IV on Day 1 of each cycle (28 days).	40 mg LY2510924 + 1500 mg Durvalumab n=3 participants at risk 40 mg LY2510924 given SQ once daily in combination with 1500 mg durvalumab given IV on Day 1 of each cycle (28 days).
Blood and lymphatic system disorders Neutropenia	0.00% 0/3 • Up To 14 months All participants who received at least one dose of study drug.	33.3% 1/3 • Number of events 1 • Up To 14 months All participants who received at least one dose of study drug.	0.00% 0/3 • Up To 14 months All participants who received at least one dose of study drug.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Pancreatic carcinoma metastatic	0.00% 0/3 • Up To 14 months All participants who received at least one dose of study drug.	0.00% 0/3 • Up To 14 months All participants who received at least one dose of study drug.	33.3% 1/3 • Number of events 1 • Up To 14 months All participants who received at least one dose of study drug.
Nervous system disorders Metabolic encephalopathy	0.00% 0/3 • Up To 14 months All participants who received at least one dose of study drug.	33.3% 1/3 • Number of events 1 • Up To 14 months All participants who received at least one dose of study drug.	0.00% 0/3 • Up To 14 months All participants who received at least one dose of study drug.
Respiratory, thoracic and mediastinal disorders Dyspnoea	0.00% 0/3 • Up To 14 months All participants who received at least one dose of study drug.	33.3% 1/3 • Number of events 1 • Up To 14 months All participants who received at least one dose of study drug.	0.00% 0/3 • Up To 14 months All participants who received at least one dose of study drug.
Vascular disorders Vena cava thrombosis	0.00% 0/3 • Up To 14 months All participants who received at least one dose of study drug.	0.00% 0/3 • Up To 14 months All participants who received at least one dose of study drug.	33.3% 1/3 • Number of events 1 • Up To 14 months All participants who received at least one dose of study drug.

Other adverse events

Additional Information

Chief Medical Officer

Eli Lilly and Company

Phone: 800-545-5979

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: GT60

Measure	20 mg LY2510924 + 1500 mg Durvalumab n=3 participants at risk 20 milligrams (mg) LY2510924 given subcutaneously (SQ) once daily in combination with 1500 mg durvalumab given intravenously (IV) on Day 1 of each cycle (28 days).	30 mg LY2510924 + 1500 mg Durvalumab n=3 participants at risk 30 mg LY2510924 given SQ once daily in combination with 1500 mg durvalumab given IV on Day 1 of each cycle (28 days).	40 mg LY2510924 + 1500 mg Durvalumab n=3 participants at risk 40 mg LY2510924 given SQ once daily in combination with 1500 mg durvalumab given IV on Day 1 of each cycle (28 days).
Blood and lymphatic system disorders Leukocytosis	0.00% 0/3 • Up To 14 months All participants who received at least one dose of study drug.	33.3% 1/3 • Number of events 1 • Up To 14 months All participants who received at least one dose of study drug.	0.00% 0/3 • Up To 14 months All participants who received at least one dose of study drug.
Cardiac disorders Sinus tachycardia	0.00% 0/3 • Up To 14 months All participants who received at least one dose of study drug.	33.3% 1/3 • Number of events 1 • Up To 14 months All participants who received at least one dose of study drug.	0.00% 0/3 • Up To 14 months All participants who received at least one dose of study drug.
Cardiac disorders Tachycardia	0.00% 0/3 • Up To 14 months All participants who received at least one dose of study drug.	0.00% 0/3 • Up To 14 months All participants who received at least one dose of study drug.	33.3% 1/3 • Number of events 1 • Up To 14 months All participants who received at least one dose of study drug.
Endocrine disorders Hyperthyroidism	0.00% 0/3 • Up To 14 months All participants who received at least one dose of study drug.	33.3% 1/3 • Number of events 1 • Up To 14 months All participants who received at least one dose of study drug.	0.00% 0/3 • Up To 14 months All participants who received at least one dose of study drug.
Endocrine disorders Hypothyroidism	0.00% 0/3 • Up To 14 months All participants who received at least one dose of study drug.	33.3% 1/3 • Number of events 2 • Up To 14 months All participants who received at least one dose of study drug.	33.3% 1/3 • Number of events 1 • Up To 14 months All participants who received at least one dose of study drug.
Eye disorders Vision blurred	0.00% 0/3 • Up To 14 months All participants who received at least one dose of study drug.	0.00% 0/3 • Up To 14 months All participants who received at least one dose of study drug.	66.7% 2/3 • Number of events 2 • Up To 14 months All participants who received at least one dose of study drug.
Gastrointestinal disorders Abdominal distension	0.00% 0/3 • Up To 14 months All participants who received at least one dose of study drug.	33.3% 1/3 • Number of events 2 • Up To 14 months All participants who received at least one dose of study drug.	0.00% 0/3 • Up To 14 months All participants who received at least one dose of study drug.
Gastrointestinal disorders Abdominal pain	0.00% 0/3 • Up To 14 months All participants who received at least one dose of study drug.	66.7% 2/3 • Number of events 2 • Up To 14 months All participants who received at least one dose of study drug.	33.3% 1/3 • Number of events 1 • Up To 14 months All participants who received at least one dose of study drug.
Gastrointestinal disorders Abdominal pain lower	0.00% 0/3 • Up To 14 months All participants who received at least one dose of study drug.	33.3% 1/3 • Number of events 1 • Up To 14 months All participants who received at least one dose of study drug.	0.00% 0/3 • Up To 14 months All participants who received at least one dose of study drug.
Gastrointestinal disorders Ascites	0.00% 0/3 • Up To 14 months All participants who received at least one dose of study drug.	33.3% 1/3 • Number of events 1 • Up To 14 months All participants who received at least one dose of study drug.	0.00% 0/3 • Up To 14 months All participants who received at least one dose of study drug.
Gastrointestinal disorders Constipation	0.00% 0/3 • Up To 14 months All participants who received at least one dose of study drug.	66.7% 2/3 • Number of events 2 • Up To 14 months All participants who received at least one dose of study drug.	0.00% 0/3 • Up To 14 months All participants who received at least one dose of study drug.
Gastrointestinal disorders Diarrhoea	33.3% 1/3 • Number of events 1 • Up To 14 months All participants who received at least one dose of study drug.	33.3% 1/3 • Number of events 1 • Up To 14 months All participants who received at least one dose of study drug.	0.00% 0/3 • Up To 14 months All participants who received at least one dose of study drug.
Gastrointestinal disorders Gastrointestinal pain	0.00% 0/3 • Up To 14 months All participants who received at least one dose of study drug.	33.3% 1/3 • Number of events 1 • Up To 14 months All participants who received at least one dose of study drug.	0.00% 0/3 • Up To 14 months All participants who received at least one dose of study drug.
Gastrointestinal disorders Nausea	0.00% 0/3 • Up To 14 months All participants who received at least one dose of study drug.	100.0% 3/3 • Number of events 4 • Up To 14 months All participants who received at least one dose of study drug.	0.00% 0/3 • Up To 14 months All participants who received at least one dose of study drug.
Gastrointestinal disorders Vomiting	0.00% 0/3 • Up To 14 months All participants who received at least one dose of study drug.	33.3% 1/3 • Number of events 2 • Up To 14 months All participants who received at least one dose of study drug.	0.00% 0/3 • Up To 14 months All participants who received at least one dose of study drug.
General disorders Chills	33.3% 1/3 • Number of events 2 • Up To 14 months All participants who received at least one dose of study drug.	33.3% 1/3 • Number of events 1 • Up To 14 months All participants who received at least one dose of study drug.	0.00% 0/3 • Up To 14 months All participants who received at least one dose of study drug.
General disorders Fatigue	0.00% 0/3 • Up To 14 months All participants who received at least one dose of study drug.	66.7% 2/3 • Number of events 2 • Up To 14 months All participants who received at least one dose of study drug.	33.3% 1/3 • Number of events 1 • Up To 14 months All participants who received at least one dose of study drug.
General disorders Injection site pain	33.3% 1/3 • Number of events 1 • Up To 14 months All participants who received at least one dose of study drug.	0.00% 0/3 • Up To 14 months All participants who received at least one dose of study drug.	0.00% 0/3 • Up To 14 months All participants who received at least one dose of study drug.
General disorders Injection site reaction	33.3% 1/3 • Number of events 1 • Up To 14 months All participants who received at least one dose of study drug.	33.3% 1/3 • Number of events 1 • Up To 14 months All participants who received at least one dose of study drug.	66.7% 2/3 • Number of events 2 • Up To 14 months All participants who received at least one dose of study drug.
General disorders Localised oedema	0.00% 0/3 • Up To 14 months All participants who received at least one dose of study drug.	0.00% 0/3 • Up To 14 months All participants who received at least one dose of study drug.	33.3% 1/3 • Number of events 1 • Up To 14 months All participants who received at least one dose of study drug.
General disorders Oedema peripheral	0.00% 0/3 • Up To 14 months All participants who received at least one dose of study drug.	33.3% 1/3 • Number of events 1 • Up To 14 months All participants who received at least one dose of study drug.	33.3% 1/3 • Number of events 2 • Up To 14 months All participants who received at least one dose of study drug.
General disorders Pyrexia	33.3% 1/3 • Number of events 2 • Up To 14 months All participants who received at least one dose of study drug.	33.3% 1/3 • Number of events 2 • Up To 14 months All participants who received at least one dose of study drug.	0.00% 0/3 • Up To 14 months All participants who received at least one dose of study drug.
Infections and infestations Bronchitis	33.3% 1/3 • Number of events 1 • Up To 14 months All participants who received at least one dose of study drug.	0.00% 0/3 • Up To 14 months All participants who received at least one dose of study drug.	0.00% 0/3 • Up To 14 months All participants who received at least one dose of study drug.
Infections and infestations Tooth infection	33.3% 1/3 • Number of events 1 • Up To 14 months All participants who received at least one dose of study drug.	0.00% 0/3 • Up To 14 months All participants who received at least one dose of study drug.	0.00% 0/3 • Up To 14 months All participants who received at least one dose of study drug.
Infections and infestations Urinary tract infection	33.3% 1/3 • Number of events 1 • Up To 14 months All participants who received at least one dose of study drug.	33.3% 1/3 • Number of events 1 • Up To 14 months All participants who received at least one dose of study drug.	0.00% 0/3 • Up To 14 months All participants who received at least one dose of study drug.
Investigations Blood alkaline phosphatase increased	33.3% 1/3 • Number of events 2 • Up To 14 months All participants who received at least one dose of study drug.	33.3% 1/3 • Number of events 1 • Up To 14 months All participants who received at least one dose of study drug.	0.00% 0/3 • Up To 14 months All participants who received at least one dose of study drug.
Investigations Blood bilirubin increased	0.00% 0/3 • Up To 14 months All participants who received at least one dose of study drug.	33.3% 1/3 • Number of events 2 • Up To 14 months All participants who received at least one dose of study drug.	0.00% 0/3 • Up To 14 months All participants who received at least one dose of study drug.
Investigations Blood creatinine increased	66.7% 2/3 • Number of events 2 • Up To 14 months All participants who received at least one dose of study drug.	0.00% 0/3 • Up To 14 months All participants who received at least one dose of study drug.	0.00% 0/3 • Up To 14 months All participants who received at least one dose of study drug.
Investigations Weight decreased	0.00% 0/3 • Up To 14 months All participants who received at least one dose of study drug.	66.7% 2/3 • Number of events 2 • Up To 14 months All participants who received at least one dose of study drug.	0.00% 0/3 • Up To 14 months All participants who received at least one dose of study drug.
Investigations White blood cell count increased	66.7% 2/3 • Number of events 2 • Up To 14 months All participants who received at least one dose of study drug.	33.3% 1/3 • Number of events 1 • Up To 14 months All participants who received at least one dose of study drug.	0.00% 0/3 • Up To 14 months All participants who received at least one dose of study drug.
Metabolism and nutrition disorders Decreased appetite	33.3% 1/3 • Number of events 1 • Up To 14 months All participants who received at least one dose of study drug.	66.7% 2/3 • Number of events 2 • Up To 14 months All participants who received at least one dose of study drug.	33.3% 1/3 • Number of events 1 • Up To 14 months All participants who received at least one dose of study drug.
Metabolism and nutrition disorders Dehydration	33.3% 1/3 • Number of events 1 • Up To 14 months All participants who received at least one dose of study drug.	33.3% 1/3 • Number of events 2 • Up To 14 months All participants who received at least one dose of study drug.	0.00% 0/3 • Up To 14 months All participants who received at least one dose of study drug.
Metabolism and nutrition disorders Hypoalbuminaemia	0.00% 0/3 • Up To 14 months All participants who received at least one dose of study drug.	33.3% 1/3 • Number of events 1 • Up To 14 months All participants who received at least one dose of study drug.	0.00% 0/3 • Up To 14 months All participants who received at least one dose of study drug.
Musculoskeletal and connective tissue disorders Back pain	0.00% 0/3 • Up To 14 months All participants who received at least one dose of study drug.	33.3% 1/3 • Number of events 1 • Up To 14 months All participants who received at least one dose of study drug.	33.3% 1/3 • Number of events 2 • Up To 14 months All participants who received at least one dose of study drug.
Musculoskeletal and connective tissue disorders Muscular weakness	0.00% 0/3 • Up To 14 months All participants who received at least one dose of study drug.	66.7% 2/3 • Number of events 2 • Up To 14 months All participants who received at least one dose of study drug.	0.00% 0/3 • Up To 14 months All participants who received at least one dose of study drug.
Nervous system disorders Disturbance in attention	33.3% 1/3 • Number of events 1 • Up To 14 months All participants who received at least one dose of study drug.	0.00% 0/3 • Up To 14 months All participants who received at least one dose of study drug.	0.00% 0/3 • Up To 14 months All participants who received at least one dose of study drug.
Nervous system disorders Dizziness	0.00% 0/3 • Up To 14 months All participants who received at least one dose of study drug.	33.3% 1/3 • Number of events 1 • Up To 14 months All participants who received at least one dose of study drug.	33.3% 1/3 • Number of events 1 • Up To 14 months All participants who received at least one dose of study drug.
Nervous system disorders Tremor	33.3% 1/3 • Number of events 1 • Up To 14 months All participants who received at least one dose of study drug.	0.00% 0/3 • Up To 14 months All participants who received at least one dose of study drug.	0.00% 0/3 • Up To 14 months All participants who received at least one dose of study drug.
Psychiatric disorders Anxiety	0.00% 0/3 • Up To 14 months All participants who received at least one dose of study drug.	0.00% 0/3 • Up To 14 months All participants who received at least one dose of study drug.	33.3% 1/3 • Number of events 1 • Up To 14 months All participants who received at least one dose of study drug.
Psychiatric disorders Confusional state	33.3% 1/3 • Number of events 1 • Up To 14 months All participants who received at least one dose of study drug.	0.00% 0/3 • Up To 14 months All participants who received at least one dose of study drug.	0.00% 0/3 • Up To 14 months All participants who received at least one dose of study drug.
Psychiatric disorders Insomnia	0.00% 0/3 • Up To 14 months All participants who received at least one dose of study drug.	33.3% 1/3 • Number of events 1 • Up To 14 months All participants who received at least one dose of study drug.	33.3% 1/3 • Number of events 1 • Up To 14 months All participants who received at least one dose of study drug.
Renal and urinary disorders Pollakiuria	33.3% 1/3 • Number of events 1 • Up To 14 months All participants who received at least one dose of study drug.	0.00% 0/3 • Up To 14 months All participants who received at least one dose of study drug.	0.00% 0/3 • Up To 14 months All participants who received at least one dose of study drug.
Respiratory, thoracic and mediastinal disorders Cough	33.3% 1/3 • Number of events 2 • Up To 14 months All participants who received at least one dose of study drug.	0.00% 0/3 • Up To 14 months All participants who received at least one dose of study drug.	0.00% 0/3 • Up To 14 months All participants who received at least one dose of study drug.
Respiratory, thoracic and mediastinal disorders Dyspnoea	0.00% 0/3 • Up To 14 months All participants who received at least one dose of study drug.	33.3% 1/3 • Number of events 1 • Up To 14 months All participants who received at least one dose of study drug.	0.00% 0/3 • Up To 14 months All participants who received at least one dose of study drug.
Skin and subcutaneous tissue disorders Alopecia	33.3% 1/3 • Number of events 1 • Up To 14 months All participants who received at least one dose of study drug.	0.00% 0/3 • Up To 14 months All participants who received at least one dose of study drug.	0.00% 0/3 • Up To 14 months All participants who received at least one dose of study drug.
Skin and subcutaneous tissue disorders Rash maculo-papular	33.3% 1/3 • Number of events 1 • Up To 14 months All participants who received at least one dose of study drug.	0.00% 0/3 • Up To 14 months All participants who received at least one dose of study drug.	0.00% 0/3 • Up To 14 months All participants who received at least one dose of study drug.
Vascular disorders Flushing	33.3% 1/3 • Number of events 1 • Up To 14 months All participants who received at least one dose of study drug.	0.00% 0/3 • Up To 14 months All participants who received at least one dose of study drug.	0.00% 0/3 • Up To 14 months All participants who received at least one dose of study drug.
Vascular disorders Hot flush	33.3% 1/3 • Number of events 2 • Up To 14 months All participants who received at least one dose of study drug.	0.00% 0/3 • Up To 14 months All participants who received at least one dose of study drug.	0.00% 0/3 • Up To 14 months All participants who received at least one dose of study drug.
Vascular disorders Hypertension	33.3% 1/3 • Number of events 1 • Up To 14 months All participants who received at least one dose of study drug.	0.00% 0/3 • Up To 14 months All participants who received at least one dose of study drug.	0.00% 0/3 • Up To 14 months All participants who received at least one dose of study drug.