Trial Outcomes & Findings for A Repeated Study of KRN23 in Adults With X-Linked Hypophosphatemia (NCT NCT01340482)

Last Updated: 2024-06-18

Results Overview

Safety and efficacy of repeated SC injections of KRN23 from baseline as assessed by serum phosphorus levels,immunogenicity, adverse events and clinically significant changes in vital signs and laboratory testing.

Recruitment status

COMPLETED

Study phase

PHASE1/PHASE2

Target enrollment

29 participants

Primary outcome timeframe

On-Treatment: 6.5 months, 27 total visits

Results posted on

2024-06-18

Participant Flow

Participant milestones

Participant milestones
Measure	Bone Substudy Placebo	KRN23 Escalating doses of KRN23 (0.05, 0.10, 0.30 and 0.60 mg/kg) will be administered SC every 28 days (up to 4 doses) KRN23: Subjects will receive escalating doses of KRN23 administered by SC injections every 28-days (up to 4 doses) based on a dosing algorithm and discretion of the investigator and sponsor.	Bone Substudy KRN23
Overall Study STARTED	1	27	1
Overall Study COMPLETED	1	25	1
Overall Study NOT COMPLETED	0	2	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Bone Substudy Placebo	KRN23 Escalating doses of KRN23 (0.05, 0.10, 0.30 and 0.60 mg/kg) will be administered SC every 28 days (up to 4 doses) KRN23: Subjects will receive escalating doses of KRN23 administered by SC injections every 28-days (up to 4 doses) based on a dosing algorithm and discretion of the investigator and sponsor.	Bone Substudy KRN23
Overall Study Adverse Event	0	2	0

Baseline Characteristics

A Repeated Study of KRN23 in Adults With X-Linked Hypophosphatemia

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	KRN23 n=27 Participants Escalating doses of KRN23 (0.05, 0.10, 0.30 and 0.60 mg/kg) will be administered SC every 28 days (up to 4 doses) KRN23: Subjects will receive escalating doses of KRN23 administered by SC injections every 28-days (up to 4 doses) based on a dosing algorithm and discretion of the investigator and sponsor.	Bone Substudy KRN23 n=1 Participants	Bone Substudy Placebo n=1 Participants	Total n=29 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Age, Categorical Between 18 and 65 years	26 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants	28 Participants n=4 Participants
Age, Categorical >=65 years	1 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants
Age, Continuous	42 years n=5 Participants	21 years n=7 Participants	28 years n=5 Participants	41 years n=4 Participants
Sex: Female, Male Female	18 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants	20 Participants n=4 Participants
Sex: Female, Male Male	9 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	9 Participants n=4 Participants
Race/Ethnicity, Customized White/Caucasian	26 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants	28 Participants n=4 Participants
Race/Ethnicity, Customized Black/African American/African Caribbean	1 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants
Region of Enrollment Canada	0 participants n=5 Participants	1 participants n=7 Participants	1 participants n=5 Participants	2 participants n=4 Participants
Region of Enrollment United States	27 participants n=5 Participants	0 participants n=7 Participants	0 participants n=5 Participants	27 participants n=4 Participants

PRIMARY outcome

Timeframe: On-Treatment: 6.5 months, 27 total visits

Outcome measures

Outcome measures
Measure	KRN23 n=27 Participants Escalating doses of KRN23 (0.05, 0.10, 0.30 and 0.60 mg/kg) will be administered SC every 28 days (up to 4 doses) KRN23: Subjects will receive escalating doses of KRN23 administered by SC injections every 28-days (up to 4 doses) based on a dosing algorithm and discretion of the investigator and sponsor.	Bone Substudy KRN23 n=1 Participants	Bone Substudy Placebo n=1 Participants
Safety and Efficacy of Repeated SC Injections of KRN23 Subjects reporting at least one TEAE	24 Participants	1 Participants	1 Participants
Safety and Efficacy of Repeated SC Injections of KRN23 Subjects who died	0 Participants	0 Participants	0 Participants
Safety and Efficacy of Repeated SC Injections of KRN23 Subjects reporting SAE other than death	0 Participants	0 Participants	0 Participants
Safety and Efficacy of Repeated SC Injections of KRN23 Subjects reporting at least one DLT	0 Participants	0 Participants	0 Participants
Safety and Efficacy of Repeated SC Injections of KRN23 Subjects reporting AE leading to discontinuation	1 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: On-Treatment: 6.5 months, 27 total visits

Population: Efficacy analysis set: All subjects who received at least 1 dose of KRN23 and completed at least one 28-day post-dose evaluation.

Effect of repeated SC injections of KRN23, from baseline, on pharmacodynamic parameters including serum phosphorus, sex hormone, bone biomarkers, quality of life assessments and population pharmacokinetics of KRN23 dose levels from cumulative dosing. Summary of serum phosphorus by visit/day is captured below.

Outcome measures

Outcome measures
Measure	KRN23 n=26 Participants Escalating doses of KRN23 (0.05, 0.10, 0.30 and 0.60 mg/kg) will be administered SC every 28 days (up to 4 doses) KRN23: Subjects will receive escalating doses of KRN23 administered by SC injections every 28-days (up to 4 doses) based on a dosing algorithm and discretion of the investigator and sponsor.	Bone Substudy KRN23	Bone Substudy Placebo
Evaluation of Effect of Repeated SC Injections of KRN23 Visit 14 (D56)/0	2.12 mg/dL Interval 1.5 to 2.7	—	—
Evaluation of Effect of Repeated SC Injections of KRN23 Visit 2 (D0)/0	1.89 mg/dL Interval 1.2 to 2.8	—	—
Evaluation of Effect of Repeated SC Injections of KRN23 Visit 3 (D3)/3	2.18 mg/dL Interval 1.5 to 2.9	—	—
Evaluation of Effect of Repeated SC Injections of KRN23 Visit 4 (D7)/7	2.20 mg/dL Interval 1.7 to 3.2	—	—
Evaluation of Effect of Repeated SC Injections of KRN23 Visit 5 (D12)/12	2.14 mg/dL Interval 1.7 to 2.7	—	—
Evaluation of Effect of Repeated SC Injections of KRN23 Visit 6 (D18)/18	2.15 mg/dL Interval 1.7 to 3.0	—	—
Evaluation of Effect of Repeated SC Injections of KRN23 Visit 7 (D26)/26	1.96 mg/dL Interval 1.4 to 2.7	—	—
Evaluation of Effect of Repeated SC Injections of KRN23 Visit 8 (D28)/0	1.93 mg/dL Interval 1.3 to 2.6	—	—
Evaluation of Effect of Repeated SC Injections of KRN23 Visit 9 (D31)/3	2.35 mg/dL Interval 1.5 to 3.3	—	—
Evaluation of Effect of Repeated SC Injections of KRN23 Visit 10 (D35)/7	2.45 mg/dL Interval 1.9 to 3.1	—	—
Evaluation of Effect of Repeated SC Injections of KRN23 Visit 11 (D40)/12	2.31 mg/dL Interval 1.6 to 3.2	—	—
Evaluation of Effect of Repeated SC Injections of KRN23 Visit 12 (D46)/18	2.28 mg/dL Interval 1.3 to 3.0	—	—
Evaluation of Effect of Repeated SC Injections of KRN23 Visit 13 (D54)/26	2.15 mg/dL Interval 1.7 to 3.0	—	—
Evaluation of Effect of Repeated SC Injections of KRN23 Visit 15 (D59)/3	2.57 mg/dL Interval 1.7 to 3.8	—	—
Evaluation of Effect of Repeated SC Injections of KRN23 Visit 16 (D63)/7	2.85 mg/dL Interval 1.9 to 3.5	—	—
Evaluation of Effect of Repeated SC Injections of KRN23 Visit 17 (D68)/12	2.83 mg/dL Interval 1.9 to 3.9	—	—
Evaluation of Effect of Repeated SC Injections of KRN23 Visit 18 (D74)/18	2.60 mg/dL Interval 1.6 to 3.5	—	—
Evaluation of Effect of Repeated SC Injections of KRN23 Visit 19 (D82)/26	2.33 mg/dL Interval 1.7 to 3.0	—	—
Evaluation of Effect of Repeated SC Injections of KRN23 Visit 20 (D84)/0	2.26 mg/dL Interval 1.8 to 3.0	—	—
Evaluation of Effect of Repeated SC Injections of KRN23 Visit 21 (D87)/3	2.64 mg/dL Interval 1.9 to 3.6	—	—
Evaluation of Effect of Repeated SC Injections of KRN23 Visit 22 (D91)/7	3.03 mg/dL Interval 2.3 to 3.7	—	—
Evaluation of Effect of Repeated SC Injections of KRN23 Visit 23 (D96)/12	2.94 mg/dL Interval 2.2 to 3.5	—	—
Evaluation of Effect of Repeated SC Injections of KRN23 Visit 24 (D102)/18	2.82 mg/dL Interval 1.7 to 4.0	—	—
Evaluation of Effect of Repeated SC Injections of KRN23 Visit 25 (D110)/26	2.54 mg/dL Interval 1.9 to 3.3	—	—
Evaluation of Effect of Repeated SC Injections of KRN23 End of Study - Visit 26 (D120)	2.22 mg/dL Interval 1.6 to 2.9	—	—
Evaluation of Effect of Repeated SC Injections of KRN23 Early Withdrawal	1.30 mg/dL Interval 1.3 to 1.3	—	—

OTHER_PRE_SPECIFIED outcome

Timeframe: On-Treatment: 6.5 months, 27 total visits

Population: Subjects randomized to the bone density substudy

Evaluation of effect of repeated SC injections of KRN23, compared to Placebo on bone mineral density and bone quality.

Outcome measures

Outcome measures
Measure	KRN23 n=1 Participants Escalating doses of KRN23 (0.05, 0.10, 0.30 and 0.60 mg/kg) will be administered SC every 28 days (up to 4 doses) KRN23: Subjects will receive escalating doses of KRN23 administered by SC injections every 28-days (up to 4 doses) based on a dosing algorithm and discretion of the investigator and sponsor.	Bone Substudy KRN23 n=1 Participants	Bone Substudy Placebo
Evaluation of Effect of Repeated SC Injections of KRN23 in Bone Substudy	NA units on a scale Peripheral quantitative CT and DXA (spine and femur) bone mineral density scans were performed for 2 subjects in the bone substudy. Due to limited sample size for KRN23 and placebo (1 subject each), no meaningful conclusion can be made.	NA units on a scale Peripheral quantitative CT and DXA (spine and femur) bone mineral density scans were performed for 2 subjects in the bone substudy. Due to limited sample size for KRN23 and placebo (1 subject each), no meaningful conclusion can be made.	—

Adverse Events

KRN23

Serious events: 0 serious events

Other events: 24 other events

Deaths: 0 deaths

Bone Substudy KRN23

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

Bone Substudy Placebo

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Additional Information

Kyowa Kirin Pharmaceutical Development

Phone: 609-919-1100

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: GT60

Other adverse events
Measure	KRN23 n=27 participants at risk Escalating doses of KRN23 (0.05, 0.10, 0.30 and 0.60 mg/kg) will be administered SC every 28 days (up to 4 doses) KRN23: Subjects will receive escalating doses of KRN23 administered by SC injections every 28-days (up to 4 doses) based on a dosing algorithm and discretion of the investigator and sponsor.	Bone Substudy KRN23 n=1 participants at risk	Bone Substudy Placebo n=1 participants at risk
Skin and subcutaneous tissue disorders Dry skin	3.7% 1/27 • Number of events 1 • Subjects were monitored for any untoward medical occurrences from the time of signed ICF through 30 days postdose.	0.00% 0/1 • Subjects were monitored for any untoward medical occurrences from the time of signed ICF through 30 days postdose.	0.00% 0/1 • Subjects were monitored for any untoward medical occurrences from the time of signed ICF through 30 days postdose.
Skin and subcutaneous tissue disorders Cold sweat	3.7% 1/27 • Number of events 1 • Subjects were monitored for any untoward medical occurrences from the time of signed ICF through 30 days postdose.	0.00% 0/1 • Subjects were monitored for any untoward medical occurrences from the time of signed ICF through 30 days postdose.	0.00% 0/1 • Subjects were monitored for any untoward medical occurrences from the time of signed ICF through 30 days postdose.
Skin and subcutaneous tissue disorders Alopecia	3.7% 1/27 • Number of events 1 • Subjects were monitored for any untoward medical occurrences from the time of signed ICF through 30 days postdose.	0.00% 0/1 • Subjects were monitored for any untoward medical occurrences from the time of signed ICF through 30 days postdose.	0.00% 0/1 • Subjects were monitored for any untoward medical occurrences from the time of signed ICF through 30 days postdose.
Vascular disorders Hypertension	3.7% 1/27 • Number of events 1 • Subjects were monitored for any untoward medical occurrences from the time of signed ICF through 30 days postdose.	0.00% 0/1 • Subjects were monitored for any untoward medical occurrences from the time of signed ICF through 30 days postdose.	0.00% 0/1 • Subjects were monitored for any untoward medical occurrences from the time of signed ICF through 30 days postdose.
Musculoskeletal and connective tissue disorders Spinal column stenosis	3.7% 1/27 • Number of events 1 • Subjects were monitored for any untoward medical occurrences from the time of signed ICF through 30 days postdose.	0.00% 0/1 • Subjects were monitored for any untoward medical occurrences from the time of signed ICF through 30 days postdose.	0.00% 0/1 • Subjects were monitored for any untoward medical occurrences from the time of signed ICF through 30 days postdose.
Musculoskeletal and connective tissue disorders Flank pain	7.4% 2/27 • Number of events 3 • Subjects were monitored for any untoward medical occurrences from the time of signed ICF through 30 days postdose.	0.00% 0/1 • Subjects were monitored for any untoward medical occurrences from the time of signed ICF through 30 days postdose.	0.00% 0/1 • Subjects were monitored for any untoward medical occurrences from the time of signed ICF through 30 days postdose.
Musculoskeletal and connective tissue disorders Exostosis	3.7% 1/27 • Number of events 1 • Subjects were monitored for any untoward medical occurrences from the time of signed ICF through 30 days postdose.	0.00% 0/1 • Subjects were monitored for any untoward medical occurrences from the time of signed ICF through 30 days postdose.	0.00% 0/1 • Subjects were monitored for any untoward medical occurrences from the time of signed ICF through 30 days postdose.
Musculoskeletal and connective tissue disorders Back pain	14.8% 4/27 • Number of events 5 • Subjects were monitored for any untoward medical occurrences from the time of signed ICF through 30 days postdose.	100.0% 1/1 • Number of events 1 • Subjects were monitored for any untoward medical occurrences from the time of signed ICF through 30 days postdose.	0.00% 0/1 • Subjects were monitored for any untoward medical occurrences from the time of signed ICF through 30 days postdose.
Musculoskeletal and connective tissue disorders Arthritis	3.7% 1/27 • Number of events 1 • Subjects were monitored for any untoward medical occurrences from the time of signed ICF through 30 days postdose.	0.00% 0/1 • Subjects were monitored for any untoward medical occurrences from the time of signed ICF through 30 days postdose.	0.00% 0/1 • Subjects were monitored for any untoward medical occurrences from the time of signed ICF through 30 days postdose.
Musculoskeletal and connective tissue disorders Arthralgia	22.2% 6/27 • Number of events 7 • Subjects were monitored for any untoward medical occurrences from the time of signed ICF through 30 days postdose.	100.0% 1/1 • Number of events 7 • Subjects were monitored for any untoward medical occurrences from the time of signed ICF through 30 days postdose.	0.00% 0/1 • Subjects were monitored for any untoward medical occurrences from the time of signed ICF through 30 days postdose.
Nervous system disorders Visual field defect	3.7% 1/27 • Number of events 1 • Subjects were monitored for any untoward medical occurrences from the time of signed ICF through 30 days postdose.	0.00% 0/1 • Subjects were monitored for any untoward medical occurrences from the time of signed ICF through 30 days postdose.	0.00% 0/1 • Subjects were monitored for any untoward medical occurrences from the time of signed ICF through 30 days postdose.
Nervous system disorders Restless legs syndrome	18.5% 5/27 • Number of events 5 • Subjects were monitored for any untoward medical occurrences from the time of signed ICF through 30 days postdose.	0.00% 0/1 • Subjects were monitored for any untoward medical occurrences from the time of signed ICF through 30 days postdose.	0.00% 0/1 • Subjects were monitored for any untoward medical occurrences from the time of signed ICF through 30 days postdose.
Nervous system disorders Presyncope	3.7% 1/27 • Number of events 1 • Subjects were monitored for any untoward medical occurrences from the time of signed ICF through 30 days postdose.	0.00% 0/1 • Subjects were monitored for any untoward medical occurrences from the time of signed ICF through 30 days postdose.	0.00% 0/1 • Subjects were monitored for any untoward medical occurrences from the time of signed ICF through 30 days postdose.
Nervous system disorders Migraine	3.7% 1/27 • Number of events 1 • Subjects were monitored for any untoward medical occurrences from the time of signed ICF through 30 days postdose.	0.00% 0/1 • Subjects were monitored for any untoward medical occurrences from the time of signed ICF through 30 days postdose.	100.0% 1/1 • Number of events 5 • Subjects were monitored for any untoward medical occurrences from the time of signed ICF through 30 days postdose.
Nervous system disorders Memory impairment	3.7% 1/27 • Number of events 1 • Subjects were monitored for any untoward medical occurrences from the time of signed ICF through 30 days postdose.	0.00% 0/1 • Subjects were monitored for any untoward medical occurrences from the time of signed ICF through 30 days postdose.	0.00% 0/1 • Subjects were monitored for any untoward medical occurrences from the time of signed ICF through 30 days postdose.
Nervous system disorders Headache	11.1% 3/27 • Number of events 4 • Subjects were monitored for any untoward medical occurrences from the time of signed ICF through 30 days postdose.	100.0% 1/1 • Number of events 4 • Subjects were monitored for any untoward medical occurrences from the time of signed ICF through 30 days postdose.	100.0% 1/1 • Number of events 2 • Subjects were monitored for any untoward medical occurrences from the time of signed ICF through 30 days postdose.
Nervous system disorders Dizziness	7.4% 2/27 • Number of events 2 • Subjects were monitored for any untoward medical occurrences from the time of signed ICF through 30 days postdose.	0.00% 0/1 • Subjects were monitored for any untoward medical occurrences from the time of signed ICF through 30 days postdose.	0.00% 0/1 • Subjects were monitored for any untoward medical occurrences from the time of signed ICF through 30 days postdose.
Nervous system disorders Disturbance in attention	7.4% 2/27 • Number of events 2 • Subjects were monitored for any untoward medical occurrences from the time of signed ICF through 30 days postdose.	0.00% 0/1 • Subjects were monitored for any untoward medical occurrences from the time of signed ICF through 30 days postdose.	0.00% 0/1 • Subjects were monitored for any untoward medical occurrences from the time of signed ICF through 30 days postdose.
Nervous system disorders Burning sensation	3.7% 1/27 • Number of events 1 • Subjects were monitored for any untoward medical occurrences from the time of signed ICF through 30 days postdose.	0.00% 0/1 • Subjects were monitored for any untoward medical occurrences from the time of signed ICF through 30 days postdose.	0.00% 0/1 • Subjects were monitored for any untoward medical occurrences from the time of signed ICF through 30 days postdose.
Pregnancy, puerperium and perinatal conditions Pregnancy	3.7% 1/27 • Number of events 1 • Subjects were monitored for any untoward medical occurrences from the time of signed ICF through 30 days postdose.	0.00% 0/1 • Subjects were monitored for any untoward medical occurrences from the time of signed ICF through 30 days postdose.	0.00% 0/1 • Subjects were monitored for any untoward medical occurrences from the time of signed ICF through 30 days postdose.
Psychiatric disorders Anxiety	7.4% 2/27 • Number of events 2 • Subjects were monitored for any untoward medical occurrences from the time of signed ICF through 30 days postdose.	0.00% 0/1 • Subjects were monitored for any untoward medical occurrences from the time of signed ICF through 30 days postdose.	0.00% 0/1 • Subjects were monitored for any untoward medical occurrences from the time of signed ICF through 30 days postdose.
Renal and urinary disorders Polyuria	3.7% 1/27 • Number of events 1 • Subjects were monitored for any untoward medical occurrences from the time of signed ICF through 30 days postdose.	0.00% 0/1 • Subjects were monitored for any untoward medical occurrences from the time of signed ICF through 30 days postdose.	0.00% 0/1 • Subjects were monitored for any untoward medical occurrences from the time of signed ICF through 30 days postdose.
Renal and urinary disorders Pollakiuria	7.4% 2/27 • Number of events 3 • Subjects were monitored for any untoward medical occurrences from the time of signed ICF through 30 days postdose.	0.00% 0/1 • Subjects were monitored for any untoward medical occurrences from the time of signed ICF through 30 days postdose.	0.00% 0/1 • Subjects were monitored for any untoward medical occurrences from the time of signed ICF through 30 days postdose.
Respiratory, thoracic and mediastinal disorders Wheezing	3.7% 1/27 • Number of events 1 • Subjects were monitored for any untoward medical occurrences from the time of signed ICF through 30 days postdose.	0.00% 0/1 • Subjects were monitored for any untoward medical occurrences from the time of signed ICF through 30 days postdose.	0.00% 0/1 • Subjects were monitored for any untoward medical occurrences from the time of signed ICF through 30 days postdose.
Respiratory, thoracic and mediastinal disorders Tonsillar hypertrophy	0.00% 0/27 • Subjects were monitored for any untoward medical occurrences from the time of signed ICF through 30 days postdose.	100.0% 1/1 • Number of events 1 • Subjects were monitored for any untoward medical occurrences from the time of signed ICF through 30 days postdose.	0.00% 0/1 • Subjects were monitored for any untoward medical occurrences from the time of signed ICF through 30 days postdose.
Respiratory, thoracic and mediastinal disorders Sinus disorder	3.7% 1/27 • Number of events 2 • Subjects were monitored for any untoward medical occurrences from the time of signed ICF through 30 days postdose.	0.00% 0/1 • Subjects were monitored for any untoward medical occurrences from the time of signed ICF through 30 days postdose.	0.00% 0/1 • Subjects were monitored for any untoward medical occurrences from the time of signed ICF through 30 days postdose.
Respiratory, thoracic and mediastinal disorders Pleurisy	3.7% 1/27 • Number of events 1 • Subjects were monitored for any untoward medical occurrences from the time of signed ICF through 30 days postdose.	0.00% 0/1 • Subjects were monitored for any untoward medical occurrences from the time of signed ICF through 30 days postdose.	0.00% 0/1 • Subjects were monitored for any untoward medical occurrences from the time of signed ICF through 30 days postdose.
Respiratory, thoracic and mediastinal disorders Painful respiration	3.7% 1/27 • Number of events 1 • Subjects were monitored for any untoward medical occurrences from the time of signed ICF through 30 days postdose.	0.00% 0/1 • Subjects were monitored for any untoward medical occurrences from the time of signed ICF through 30 days postdose.	0.00% 0/1 • Subjects were monitored for any untoward medical occurrences from the time of signed ICF through 30 days postdose.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	0.00% 0/27 • Subjects were monitored for any untoward medical occurrences from the time of signed ICF through 30 days postdose.	100.0% 1/1 • Number of events 1 • Subjects were monitored for any untoward medical occurrences from the time of signed ICF through 30 days postdose.	0.00% 0/1 • Subjects were monitored for any untoward medical occurrences from the time of signed ICF through 30 days postdose.
Skin and subcutaneous tissue disorders Swelling face	3.7% 1/27 • Number of events 1 • Subjects were monitored for any untoward medical occurrences from the time of signed ICF through 30 days postdose.	0.00% 0/1 • Subjects were monitored for any untoward medical occurrences from the time of signed ICF through 30 days postdose.	0.00% 0/1 • Subjects were monitored for any untoward medical occurrences from the time of signed ICF through 30 days postdose.
Blood and lymphatic system disorders Iron deficiency anaemia	3.7% 1/27 • Number of events 1 • Subjects were monitored for any untoward medical occurrences from the time of signed ICF through 30 days postdose.	0.00% 0/1 • Subjects were monitored for any untoward medical occurrences from the time of signed ICF through 30 days postdose.	0.00% 0/1 • Subjects were monitored for any untoward medical occurrences from the time of signed ICF through 30 days postdose.
Ear and labyrinth disorders Ear pain	0.00% 0/27 • Subjects were monitored for any untoward medical occurrences from the time of signed ICF through 30 days postdose.	100.0% 1/1 • Number of events 1 • Subjects were monitored for any untoward medical occurrences from the time of signed ICF through 30 days postdose.	0.00% 0/1 • Subjects were monitored for any untoward medical occurrences from the time of signed ICF through 30 days postdose.
Gastrointestinal disorders Gastrooesophageal reflux disease	3.7% 1/27 • Number of events 2 • Subjects were monitored for any untoward medical occurrences from the time of signed ICF through 30 days postdose.	0.00% 0/1 • Subjects were monitored for any untoward medical occurrences from the time of signed ICF through 30 days postdose.	0.00% 0/1 • Subjects were monitored for any untoward medical occurrences from the time of signed ICF through 30 days postdose.
Gastrointestinal disorders Abdominal pain upper	7.4% 2/27 • Number of events 2 • Subjects were monitored for any untoward medical occurrences from the time of signed ICF through 30 days postdose.	0.00% 0/1 • Subjects were monitored for any untoward medical occurrences from the time of signed ICF through 30 days postdose.	0.00% 0/1 • Subjects were monitored for any untoward medical occurrences from the time of signed ICF through 30 days postdose.
Gastrointestinal disorders Dyspepsia	7.4% 2/27 • Number of events 4 • Subjects were monitored for any untoward medical occurrences from the time of signed ICF through 30 days postdose.	100.0% 1/1 • Number of events 1 • Subjects were monitored for any untoward medical occurrences from the time of signed ICF through 30 days postdose.	0.00% 0/1 • Subjects were monitored for any untoward medical occurrences from the time of signed ICF through 30 days postdose.
Gastrointestinal disorders Constipation	3.7% 1/27 • Number of events 1 • Subjects were monitored for any untoward medical occurrences from the time of signed ICF through 30 days postdose.	0.00% 0/1 • Subjects were monitored for any untoward medical occurrences from the time of signed ICF through 30 days postdose.	0.00% 0/1 • Subjects were monitored for any untoward medical occurrences from the time of signed ICF through 30 days postdose.
Gastrointestinal disorders Diarrhoea	18.5% 5/27 • Number of events 6 • Subjects were monitored for any untoward medical occurrences from the time of signed ICF through 30 days postdose.	0.00% 0/1 • Subjects were monitored for any untoward medical occurrences from the time of signed ICF through 30 days postdose.	0.00% 0/1 • Subjects were monitored for any untoward medical occurrences from the time of signed ICF through 30 days postdose.
Gastrointestinal disorders Nausea	7.4% 2/27 • Number of events 5 • Subjects were monitored for any untoward medical occurrences from the time of signed ICF through 30 days postdose.	0.00% 0/1 • Subjects were monitored for any untoward medical occurrences from the time of signed ICF through 30 days postdose.	0.00% 0/1 • Subjects were monitored for any untoward medical occurrences from the time of signed ICF through 30 days postdose.
Gastrointestinal disorders Mouth ulceration	0.00% 0/27 • Subjects were monitored for any untoward medical occurrences from the time of signed ICF through 30 days postdose.	100.0% 1/1 • Number of events 1 • Subjects were monitored for any untoward medical occurrences from the time of signed ICF through 30 days postdose.	0.00% 0/1 • Subjects were monitored for any untoward medical occurrences from the time of signed ICF through 30 days postdose.
Gastrointestinal disorders Toothache	3.7% 1/27 • Number of events 2 • Subjects were monitored for any untoward medical occurrences from the time of signed ICF through 30 days postdose.	0.00% 0/1 • Subjects were monitored for any untoward medical occurrences from the time of signed ICF through 30 days postdose.	0.00% 0/1 • Subjects were monitored for any untoward medical occurrences from the time of signed ICF through 30 days postdose.