Trial Outcomes & Findings for A Study to Assess Efficacy/Safety of Ladarixin in Type 1 Diabetes Patients With Preserved ß-cell Function at Baseline. (NCT NCT04899271)

Last Updated: 2025-05-14

Results Overview

The sample size of the study is calculated on the "proportion of patients with a HbA1c \< 7% and daily insulin requirement \<0.50 IU/Kg/day", a post-hoc composite endpoint derived from data of the phase 2 trial (MEX0114), considering a larger effect size expected from the longer treatment length (one year versus 3 months). The time frame for the primary endpoint has been set at Month 12 (Week 52) in order to evaluate the potential of ladarixin effects on a long-term projection. Please note that "proportion" is expressed as "count" (number + % of participants)

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

25 participants

Primary outcome timeframe

Month 12 (52±2 weeks)

Results posted on

2025-05-14

Participant Flow

The number of patients randomized and treated was lower than planned in the study protocol. The Sponsor decided to stop patient enrolment on 28 March 2022, due to the recruitment rate being lower than expected. At the time of recruitment closure, 25 patients had been randomized compared with the 75 planned.

Overall, 80 participants were screened, having signed the informed consent form. Out of these, 52 participants (65.0%) did not meet eligibility criteria (screen failure) and 3 participants (3.8%) withdrew their consent, making a total of 55 participants (68.8%) not enrolled and thus not randomized.

Participant milestones

Participant milestones
Measure	Ladarixin The treatment group will receive 400 mg b.i.d. for 13 cycles of 14 days on/14 days off) Ladarixin: 400 mg b.i.d. for 13 cycles of 14 days on/14 days off	Placebo The control group will receive matched placebo Placebo: Placebo will be administered orally with the same scheme of administration of LDX to preserve blinding
Overall Study STARTED	18	7
Overall Study Received IMP	18	7
Overall Study FAS Population	18	7
Overall Study SAF Population	18	7
Overall Study Completed Week 11 Visit (End of Cycle 3),	17	7
Overall Study Completed Week 23 Visit (End of Cycle 6)	16	7
Overall Study Completed Month 6 Visit,	16	7
Overall Study Completed Week 35 Visit (End of Cycle 9)	15	7
Overall Study Completed Month 12 Visit (End of Cycle 13),	15	7
Overall Study COMPLETED	15	7
Overall Study NOT COMPLETED	3	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Ladarixin The treatment group will receive 400 mg b.i.d. for 13 cycles of 14 days on/14 days off) Ladarixin: 400 mg b.i.d. for 13 cycles of 14 days on/14 days off	Placebo The control group will receive matched placebo Placebo: Placebo will be administered orally with the same scheme of administration of LDX to preserve blinding
Overall Study Lost to Follow-up	1	0
Overall Study Subject request/consent withdrawal	2	0

Baseline Characteristics

A Study to Assess Efficacy/Safety of Ladarixin in Type 1 Diabetes Patients With Preserved ß-cell Function at Baseline.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Ladarixin n=18 Participants The treatment group received 400 mg b.i.d. for 13 cycles of 14 days on/14 days off) Ladarixin: 400 mg b.i.d. for 13 cycles of 14 days on/14 days off	Placebo n=7 Participants The control group received matched placebo Placebo: Placebo was administered orally with the same scheme of administration of LDX to preserve blinding	Total n=25 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Age, Categorical Between 18 and 65 years	18 Participants n=93 Participants	7 Participants n=4 Participants	25 Participants n=27 Participants
Age, Categorical >=65 years	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Age, Continuous	25.5 years STANDARD_DEVIATION 7.6 • n=93 Participants	27.3 years STANDARD_DEVIATION 7.7 • n=4 Participants	26.0 years STANDARD_DEVIATION 7.5 • n=27 Participants
Sex: Female, Male Female	6 Participants n=93 Participants	2 Participants n=4 Participants	8 Participants n=27 Participants
Sex: Female, Male Male	12 Participants n=93 Participants	5 Participants n=4 Participants	17 Participants n=27 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Race (NIH/OMB) Asian	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Race (NIH/OMB) Black or African American	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Race (NIH/OMB) White	18 Participants n=93 Participants	7 Participants n=4 Participants	25 Participants n=27 Participants
Race (NIH/OMB) More than one race	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Region of Enrollment United States	1 participants n=93 Participants	1 participants n=4 Participants	2 participants n=27 Participants
Region of Enrollment Italy	8 participants n=93 Participants	3 participants n=4 Participants	11 participants n=27 Participants
Region of Enrollment Serbia	5 participants n=93 Participants	1 participants n=4 Participants	6 participants n=27 Participants
Region of Enrollment Germany	4 participants n=93 Participants	2 participants n=4 Participants	6 participants n=27 Participants

PRIMARY outcome

Timeframe: Month 12 (52±2 weeks)

Population: FAS: The Full Analysis Set consisted of all randomized patients who received at least one dose of the IMP (either ladarixin or placebo). The FAS was analyzed according to the ITT principle, i.e., by treatment allocation regardless happening of intercurrent events (treatment policy strategy). The FAS was used for the primary analyses of the study and to present results on efficacy data.

Outcome measures

Outcome measures
Measure	Ladarixin n=18 Participants The treatment group will receive 400 mg b.i.d. for 13 cycles of 14 days on/14 days off) Ladarixin: 400 mg b.i.d. for 13 cycles of 14 days on/14 days off	Placebo n=7 Participants The control group will receive matched placebo Placebo: Placebo will be administered orally with the same scheme of administration of LDX to preserve blinding
Number of Patients With HbA1c <7% and Daily Insulin Requirement <0.50 IU/Kg/Day at Month 12	11 Participants	5 Participants

SECONDARY outcome

Timeframe: Month 6 (26±2 weeks) and Month 18 (78±2 weeks)

The sample size of the study is calculated on the "proportion of patients with a HbA1c \< 7% and daily insulin requirement \<0.50 IU/Kg/day", a post-hoc composite endpoint derived from data of the phase 2 trial (MEX0114), considering a larger effect size expected from the longer treatment length (one year versus 3 months). Follow-up is extended up to 18 months to evaluate the potential persistency of any glycemic benefit. Please note that "proportion" is expressed as "count" (number + % of participants)

Outcome measures

Outcome measures
Measure	Ladarixin n=18 Participants The treatment group will receive 400 mg b.i.d. for 13 cycles of 14 days on/14 days off) Ladarixin: 400 mg b.i.d. for 13 cycles of 14 days on/14 days off	Placebo n=7 Participants The control group will receive matched placebo Placebo: Placebo will be administered orally with the same scheme of administration of LDX to preserve blinding
Number of Patients With HbA1c < 7% and Daily Insulin Requirement <0.50 IU/Kg/Day at Months 6 and 18 Month 6	12 Participants	6 Participants
Number of Patients With HbA1c < 7% and Daily Insulin Requirement <0.50 IU/Kg/Day at Months 6 and 18 Month 18	8 Participants	5 Participants

SECONDARY outcome

Timeframe: Months 6 (26±2 weeks), 12 (52±2 weeks) and 18 (78±2 weeks )

The number of patients with a reduction in HbA1c% \> 0.5% from baseline and daily insulin requirement \<0.50 IU/Kg/day was calculated at the hereunder specified timepoints.

Outcome measures

Outcome measures
Measure	Ladarixin n=18 Participants The treatment group will receive 400 mg b.i.d. for 13 cycles of 14 days on/14 days off) Ladarixin: 400 mg b.i.d. for 13 cycles of 14 days on/14 days off	Placebo n=7 Participants The control group will receive matched placebo Placebo: Placebo will be administered orally with the same scheme of administration of LDX to preserve blinding
Number of Patients With a Reduction in HbA1c% > 0.5% From Baseline and Daily Insulin Requirement <0.50 IU/Kg/Day at Months 6, 12 and 18 Month 12	8 Participants	3 Participants
Number of Patients With a Reduction in HbA1c% > 0.5% From Baseline and Daily Insulin Requirement <0.50 IU/Kg/Day at Months 6, 12 and 18 Month 6	8 Participants	4 Participants
Number of Patients With a Reduction in HbA1c% > 0.5% From Baseline and Daily Insulin Requirement <0.50 IU/Kg/Day at Months 6, 12 and 18 Month 18	6 Participants	2 Participants

SECONDARY outcome

Timeframe: Months 6 (26±2 weeks), 12 (52±2 weeks) and 18 (78±2 weeks)

Population: FAS (Full Analysis Set): all randomized patients who received at least one dose of the IMP (either ladarixin or placebo), analyzed according to the ITT principle. Discrepancies between Overall Number of Participants Analyzed and Number Analyzed for Ladarixin group due to: at Month 6: 2 participants withdrew their consent; at Month 12: 1 additional participant was lost at follow-up (who remained lost at follow-up even for Month 18 visit).

C-peptide level is a widely used measure of pancreatic beta-cell function and the MMTT is one of the methods for its estimation. AUC stands for Area Under the Curve. AUC calculation was based on actual rather scheduled timings and it was calculated using the trapezoidal rule. C-peptide 0-120 min AUC (nmol/L) values were calculated based on all Basal-120min C-peptide values. Unscheduled assessments were excluded from the analysis.

Outcome measures

Outcome measures
Measure	Ladarixin n=16 Participants The treatment group will receive 400 mg b.i.d. for 13 cycles of 14 days on/14 days off) Ladarixin: 400 mg b.i.d. for 13 cycles of 14 days on/14 days off	Placebo n=7 Participants The control group will receive matched placebo Placebo: Placebo will be administered orally with the same scheme of administration of LDX to preserve blinding
Change From Baseline in 2-hour AUC of C-peptide Response to the MMTT at Months 6, 12 and 18 Month 6	-7.17 nmol/L Standard Deviation 19.33	-12.70 nmol/L Standard Deviation 16.87
Change From Baseline in 2-hour AUC of C-peptide Response to the MMTT at Months 6, 12 and 18 Month 12	0.25 nmol/L Standard Deviation 23.77	-0.88 nmol/L Standard Deviation 53.61
Change From Baseline in 2-hour AUC of C-peptide Response to the MMTT at Months 6, 12 and 18 Month 18	-2.07 nmol/L Standard Deviation 20.79	-5.41 nmol/L Standard Deviation 32.52

SECONDARY outcome

Timeframe: Months 6 (26±2 weeks), 12 (52±2 weeks) and 18 (78±2 weeks)

Population: FAS (Full Analysis Set): all randomized patients who received at least one dose of the IMP (either ladarixin or placebo), analyzed according to the ITT principle. Discrepancies between Overall Number of Participants Analyzed and Number Analyzed in both arms are due to participants withdrawing consent or with blood samples not collected at timepoints or lost at follow-up.

HbA1c measurement can be used as a diagnostic test for diabetes providing that stringent quality assurance tests are in place and assays are standardised to criteria aligned to the international reference values, and there are no conditions present which preclude its accurate measurement. An HbA1c of 6.5% is recommended as the cut point for diagnosing diabetes. A value of less than 6.5% does not exclude diabetes diagnosed using glucose tests. An A1C test measures the percentage of red blood cells that have glucose-coated hemoglobin.

Outcome measures

Outcome measures
Measure	Ladarixin n=15 Participants The treatment group will receive 400 mg b.i.d. for 13 cycles of 14 days on/14 days off) Ladarixin: 400 mg b.i.d. for 13 cycles of 14 days on/14 days off	Placebo n=7 Participants The control group will receive matched placebo Placebo: Placebo will be administered orally with the same scheme of administration of LDX to preserve blinding
Changes From Baseline in Percentage Glycated Hemoglobin (HbA1c) Levels at Months 6, 12 and 18 Month 6	-0.67 percentage HbA1c Standard Deviation 0.88	-0.84 percentage HbA1c Standard Deviation 1.11
Changes From Baseline in Percentage Glycated Hemoglobin (HbA1c) Levels at Months 6, 12 and 18 Month 12	-0.51 percentage HbA1c Standard Deviation 1.24	-0.77 percentage HbA1c Standard Deviation 1.28
Changes From Baseline in Percentage Glycated Hemoglobin (HbA1c) Levels at Months 6, 12 and 18 Month 18	-0.30 percentage HbA1c Standard Deviation 1.55	-0.33 percentage HbA1c Standard Deviation 0.67

SECONDARY outcome

Timeframe: Months 6 (26±2 weeks), 12 (52±2 weeks) and 18 (78±2 weeks)

Population: FAS (Full Analysis Set): all randomized patients who received at least one dose of the IMP (either ladarixin or placebo), analyzed according to the ITT principle. Discrepancies between Overall Number of Participants Analyzed and Number Analyzed in both arms are due to participants withdrawing consent or with blood samples not collected at timepoints or lost at follow-up.

For the purpose of this study, a severe hypoglycaemic event is defined as an event with one of the following symptoms: memory loss, confusion, uncontrollable behavior, irrational behavior, unusual difficulty in awakening, suspected seizure, seizure, loss of consciousness or visual symptoms, in which the subject was unable to treat him/herself and which was associated with either a blood glucose level \<54mg/dL (3.0 mmol/L) or prompt recovery after oral carbohydrate, i.v. glucose, or glucagon administration.

Outcome measures

Outcome measures
Measure	Ladarixin n=15 Participants The treatment group will receive 400 mg b.i.d. for 13 cycles of 14 days on/14 days off) Ladarixin: 400 mg b.i.d. for 13 cycles of 14 days on/14 days off	Placebo n=7 Participants The control group will receive matched placebo Placebo: Placebo will be administered orally with the same scheme of administration of LDX to preserve blinding
Number of Patients With HbA1c < 7% Who Did Not Experience Severe Hypoglycemic Events During Treatment at Months 6,12 and 18 Month 18	7 Participants	2 Participants
Number of Patients With HbA1c < 7% Who Did Not Experience Severe Hypoglycemic Events During Treatment at Months 6,12 and 18 Month 6	7 Participants	3 Participants
Number of Patients With HbA1c < 7% Who Did Not Experience Severe Hypoglycemic Events During Treatment at Months 6,12 and 18 Month 12	8 Participants	3 Participants

SECONDARY outcome

Timeframe: From baseline to study termination (month 18, week 78)

Population: FAS: The Full Analysis Set consisted of all randomized patients who received at least one dose of the IMP. The FAS was analyzed according to the ITT principle, i.e., by treatment allocation regardless happening of intercurrent events (treatment policy strategy). The FAS was used for the primary analyses of the study and to present results on efficacy data.

Outcome measures

Outcome measures
Measure	Ladarixin n=18 Participants The treatment group will receive 400 mg b.i.d. for 13 cycles of 14 days on/14 days off) Ladarixin: 400 mg b.i.d. for 13 cycles of 14 days on/14 days off	Placebo n=7 Participants The control group will receive matched placebo Placebo: Placebo will be administered orally with the same scheme of administration of LDX to preserve blinding
Overall Number of Self-reported Episodes of Severe Hypoglycemia	28 total number of severe hypoglyc episodes	8 total number of severe hypoglyc episodes

SECONDARY outcome

Timeframe: Months 6 (week 26±2), 12 (week 52±2) and 18 (week 78±2)

A severe hypoglycemic event was defined as an event with 1 of the following symptoms: "memory loss, confusion, uncontrollable behavior, irrational behavior, unusual difficulty in awakening, suspected seizure, seizure, loss of consciousness, or visual symptoms", in which the subject was unable to treat him/herself and which was associated with either a blood glucose level \<54mg/dL or prompt recovery after oral carbohydrate, i.e. glucose, or glucagon administration. Summary statistics of blood glucose level (mg/dL) are provided by treatment group at each time point for patients reporting severe hypoglycemia.

Outcome measures

Outcome measures
Measure	Ladarixin n=18 Participants The treatment group will receive 400 mg b.i.d. for 13 cycles of 14 days on/14 days off) Ladarixin: 400 mg b.i.d. for 13 cycles of 14 days on/14 days off	Placebo n=7 Participants The control group will receive matched placebo Placebo: Placebo will be administered orally with the same scheme of administration of LDX to preserve blinding
Blood Glucose Levels for Patients Reporting Severe Hypoglycemia at Months 6, 12 and 18 Month 6	48.11 mg/dL Standard Deviation 4.73	51.00 mg/dL Standard Deviation 3.94
Blood Glucose Levels for Patients Reporting Severe Hypoglycemia at Months 6, 12 and 18 Month 12	48.71 mg/dL Standard Deviation 4.75	49.57 mg/dL Standard Deviation 5.71
Blood Glucose Levels for Patients Reporting Severe Hypoglycemia at Months 6, 12 and 18 Month 18	48.27 mg/dL Standard Deviation 4.90	50.13 mg/dL Standard Deviation 5.51

SECONDARY outcome

Timeframe: Months 6 (26±2 weeks), 12 (52±2 weeks) and 18 (78±2 weeks)

Population: FAS (Full Analysis Set): all randomized patients who received at least one dose of the IMP (either ladarixin or placebo), analyzed according to the ITT principle. Discrepancies between Overall Number of Participants Analyzed and Number Analyzed in both arms are due to participants withdrawing consent or with blood samples not collected at timepoints or lost at follow-up

For the purpose of this study, daily insulin is averaged over the previous 3 days.Insulin requirement (IU/kg/day averaged over the previous 3 days) was to be recorded to Months 6, 12 and 18. Patients were admitted to intensive diabetes management, according to current ADA recommendation \[2014\]. Patients were instructed to self-monitor their glucose values at least 4 times a day and to report (glucose meter/log) outcome to the diabetes management team. Insulin intake was adjusted to target HbA1c levels of less than 7% and self-monitored (fingerstick): * pre-prandial blood glucose of 70-130 mg/dL * post-prandial blood glucose \< 180 mg/dL * bed-time blood glucose of 110-150 mg/dL

Outcome measures

Outcome measures
Measure	Ladarixin n=16 Participants The treatment group will receive 400 mg b.i.d. for 13 cycles of 14 days on/14 days off) Ladarixin: 400 mg b.i.d. for 13 cycles of 14 days on/14 days off	Placebo n=7 Participants The control group will receive matched placebo Placebo: Placebo will be administered orally with the same scheme of administration of LDX to preserve blinding
Change From Baseline in Average (Previous 3 Days) Daily Insulin Requirements (IU/kg/Day) at Months 6,12 and 18 Month 6	-0.209 IU/kg/day Standard Deviation 0.644	-0.028 IU/kg/day Standard Deviation 0.228
Change From Baseline in Average (Previous 3 Days) Daily Insulin Requirements (IU/kg/Day) at Months 6,12 and 18 Month 12	-0.183 IU/kg/day Standard Deviation 0.661	0.024 IU/kg/day Standard Deviation 0.271
Change From Baseline in Average (Previous 3 Days) Daily Insulin Requirements (IU/kg/Day) at Months 6,12 and 18 Month 18	-0.183 IU/kg/day Standard Deviation 0.639	-0.005 IU/kg/day Standard Deviation 0.342

SECONDARY outcome

Timeframe: Months 6 (26±2 weeks), 12 (52±2 weeks) and 18 (78±2 weeks)

Population: FAS (Full Analysis Set): all randomized patients who received at least one dose of the IMP (either ladarixin or placebo), analyzed according to the ITT principle. Discrepancies between Overall Number of Participants Analyzed and Number Analyzed in both arms are due to participants withdrawing consent or with blood samples not collected at timepoints or lost at follow-up.

Estimated Glucose Disposal Rate (eGDR) is a marker for the Assessment of Insulin Resistance and a validated clinical tool for estimating insulin sensitivity in type 1 diabetes.

Outcome measures

Outcome measures
Measure	Ladarixin n=15 Participants The treatment group will receive 400 mg b.i.d. for 13 cycles of 14 days on/14 days off) Ladarixin: 400 mg b.i.d. for 13 cycles of 14 days on/14 days off	Placebo n=7 Participants The control group will receive matched placebo Placebo: Placebo will be administered orally with the same scheme of administration of LDX to preserve blinding
Change From Baseline in Estimated Glucose Disposal Rate (eGDR) at Months 6, 12 and 18 Month 6	0.418 mg/kg/min Standard Deviation 0.815	0.367 mg/kg/min Standard Deviation 0.816
Change From Baseline in Estimated Glucose Disposal Rate (eGDR) at Months 6, 12 and 18 Month 12	0.067 mg/kg/min Standard Deviation 1.504	0.623 mg/kg/min Standard Deviation 0.862
Change From Baseline in Estimated Glucose Disposal Rate (eGDR) at Months 6, 12 and 18 Month 18	0.242 mg/kg/min Standard Deviation 1.142	-0.238 mg/kg/min Standard Deviation 1.255

SECONDARY outcome

Timeframe: Throughout the study up to 18 months

Population: SAF population: The Safety (SAF) population consisted of all randomized patients who received at least one dose of the IMP. The SAF population was analyzed according to the actual treatment received and was used to present results on safety data.

An AE is any untoward medical occurrence in a participant, which does not necessarily have a causal relationship with the trial intervention. A serious adverse event is an adverse event that results in death, is life-threatening, requires hospitalisation or prolongation of existing hospitalisation, results in persistent or significant disability or incapacity, or is a birth defect.

Outcome measures

Outcome measures
Measure	Ladarixin n=18 Participants The treatment group will receive 400 mg b.i.d. for 13 cycles of 14 days on/14 days off) Ladarixin: 400 mg b.i.d. for 13 cycles of 14 days on/14 days off	Placebo n=7 Participants The control group will receive matched placebo Placebo: Placebo will be administered orally with the same scheme of administration of LDX to preserve blinding
Number of Patients With at Least One Adverse Events (AEs), Serious or Not Serious any TEAE	12 Participants	5 Participants
Number of Patients With at Least One Adverse Events (AEs), Serious or Not Serious serious TEAE	1 Participants	0 Participants
Number of Patients With at Least One Adverse Events (AEs), Serious or Not Serious non-serious TEAE	12 Participants	5 Participants
Number of Patients With at Least One Adverse Events (AEs), Serious or Not Serious TEAEs leading to IMP discontinuation	1 Participants	1 Participants
Number of Patients With at Least One Adverse Events (AEs), Serious or Not Serious TEAEs leading to death	0 Participants	0 Participants

Adverse Events

Ladarixin

Serious events: 1 serious events

Other events: 12 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 5 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Ladarixin n=18 participants at risk The treatment group will receive 400 mg b.i.d. for 13 cycles of 14 days on/14 days off) Ladarixin: 400 mg b.i.d. for 13 cycles of 14 days on/14 days off	Placebo n=7 participants at risk The control group will receive matched placebo Placebo: Placebo will be administered orally with the same scheme of administration of LDX to preserve blinding
Endocrine disorders primary hyperparathyroidism	5.6% 1/18 • Number of events 3 • Throughout the study, from the baseline to the study termination (from cycle 1 up to Month 12) and follow-up (Month 18)	0.00% 0/7 • Throughout the study, from the baseline to the study termination (from cycle 1 up to Month 12) and follow-up (Month 18)

Other adverse events

Additional Information

Clinical Development and Operations

Dompé Farmaceutici SpA

Phone: +39 (0) 583831

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Ladarixin n=18 participants at risk The treatment group will receive 400 mg b.i.d. for 13 cycles of 14 days on/14 days off) Ladarixin: 400 mg b.i.d. for 13 cycles of 14 days on/14 days off	Placebo n=7 participants at risk The control group will receive matched placebo Placebo: Placebo will be administered orally with the same scheme of administration of LDX to preserve blinding
Infections and infestations COVID-19	33.3% 6/18 • Number of events 6 • Throughout the study, from the baseline to the study termination (from cycle 1 up to Month 12) and follow-up (Month 18)	71.4% 5/7 • Number of events 5 • Throughout the study, from the baseline to the study termination (from cycle 1 up to Month 12) and follow-up (Month 18)
Infections and infestations Nasopharyngitis	11.1% 2/18 • Number of events 5 • Throughout the study, from the baseline to the study termination (from cycle 1 up to Month 12) and follow-up (Month 18)	14.3% 1/7 • Number of events 1 • Throughout the study, from the baseline to the study termination (from cycle 1 up to Month 12) and follow-up (Month 18)
Infections and infestations Influenza	5.6% 1/18 • Number of events 1 • Throughout the study, from the baseline to the study termination (from cycle 1 up to Month 12) and follow-up (Month 18)	0.00% 0/7 • Throughout the study, from the baseline to the study termination (from cycle 1 up to Month 12) and follow-up (Month 18)
Infections and infestations Nasal herpes	5.6% 1/18 • Number of events 1 • Throughout the study, from the baseline to the study termination (from cycle 1 up to Month 12) and follow-up (Month 18)	0.00% 0/7 • Throughout the study, from the baseline to the study termination (from cycle 1 up to Month 12) and follow-up (Month 18)
Infections and infestations Streptococcal urinary tract infection	0.00% 0/18 • Throughout the study, from the baseline to the study termination (from cycle 1 up to Month 12) and follow-up (Month 18)	14.3% 1/7 • Number of events 1 • Throughout the study, from the baseline to the study termination (from cycle 1 up to Month 12) and follow-up (Month 18)
Infections and infestations Vulvovaginal candidiasis	0.00% 0/18 • Throughout the study, from the baseline to the study termination (from cycle 1 up to Month 12) and follow-up (Month 18)	28.6% 2/7 • Number of events 2 • Throughout the study, from the baseline to the study termination (from cycle 1 up to Month 12) and follow-up (Month 18)
Gastrointestinal disorders Dyspepsia	11.1% 2/18 • Number of events 2 • Throughout the study, from the baseline to the study termination (from cycle 1 up to Month 12) and follow-up (Month 18)	0.00% 0/7 • Throughout the study, from the baseline to the study termination (from cycle 1 up to Month 12) and follow-up (Month 18)
Gastrointestinal disorders Abnormal faeces	5.6% 1/18 • Number of events 1 • Throughout the study, from the baseline to the study termination (from cycle 1 up to Month 12) and follow-up (Month 18)	0.00% 0/7 • Throughout the study, from the baseline to the study termination (from cycle 1 up to Month 12) and follow-up (Month 18)
Gastrointestinal disorders Diarrhea	5.6% 1/18 • Number of events 1 • Throughout the study, from the baseline to the study termination (from cycle 1 up to Month 12) and follow-up (Month 18)	0.00% 0/7 • Throughout the study, from the baseline to the study termination (from cycle 1 up to Month 12) and follow-up (Month 18)
Gastrointestinal disorders Gastrointestinal disorder	5.6% 1/18 • Number of events 1 • Throughout the study, from the baseline to the study termination (from cycle 1 up to Month 12) and follow-up (Month 18)	0.00% 0/7 • Throughout the study, from the baseline to the study termination (from cycle 1 up to Month 12) and follow-up (Month 18)
Gastrointestinal disorders Irritable bowel syndrome	5.6% 1/18 • Number of events 1 • Throughout the study, from the baseline to the study termination (from cycle 1 up to Month 12) and follow-up (Month 18)	0.00% 0/7 • Throughout the study, from the baseline to the study termination (from cycle 1 up to Month 12) and follow-up (Month 18)
Gastrointestinal disorders abdominal pain	0.00% 0/18 • Throughout the study, from the baseline to the study termination (from cycle 1 up to Month 12) and follow-up (Month 18)	14.3% 1/7 • Number of events 1 • Throughout the study, from the baseline to the study termination (from cycle 1 up to Month 12) and follow-up (Month 18)
Gastrointestinal disorders Nausea	0.00% 0/18 • Throughout the study, from the baseline to the study termination (from cycle 1 up to Month 12) and follow-up (Month 18)	42.9% 3/7 • Number of events 3 • Throughout the study, from the baseline to the study termination (from cycle 1 up to Month 12) and follow-up (Month 18)
Metabolism and nutrition disorders Hyperglycemia	11.1% 2/18 • Number of events 2 • Throughout the study, from the baseline to the study termination (from cycle 1 up to Month 12) and follow-up (Month 18)	0.00% 0/7 • Throughout the study, from the baseline to the study termination (from cycle 1 up to Month 12) and follow-up (Month 18)
Metabolism and nutrition disorders Hypoglycemia	11.1% 2/18 • Number of events 8 • Throughout the study, from the baseline to the study termination (from cycle 1 up to Month 12) and follow-up (Month 18)	14.3% 1/7 • Number of events 1 • Throughout the study, from the baseline to the study termination (from cycle 1 up to Month 12) and follow-up (Month 18)
Endocrine disorders Autoimmune thyroiditis	5.6% 1/18 • Number of events 1 • Throughout the study, from the baseline to the study termination (from cycle 1 up to Month 12) and follow-up (Month 18)	14.3% 1/7 • Number of events 1 • Throughout the study, from the baseline to the study termination (from cycle 1 up to Month 12) and follow-up (Month 18)
Endocrine disorders Hyperparathyroidism primary	5.6% 1/18 • Number of events 3 • Throughout the study, from the baseline to the study termination (from cycle 1 up to Month 12) and follow-up (Month 18)	0.00% 0/7 • Throughout the study, from the baseline to the study termination (from cycle 1 up to Month 12) and follow-up (Month 18)
Injury, poisoning and procedural complications Contusion	5.6% 1/18 • Number of events 1 • Throughout the study, from the baseline to the study termination (from cycle 1 up to Month 12) and follow-up (Month 18)	0.00% 0/7 • Throughout the study, from the baseline to the study termination (from cycle 1 up to Month 12) and follow-up (Month 18)
Injury, poisoning and procedural complications Post procedural hypothyroidism	5.6% 1/18 • Number of events 1 • Throughout the study, from the baseline to the study termination (from cycle 1 up to Month 12) and follow-up (Month 18)	0.00% 0/7 • Throughout the study, from the baseline to the study termination (from cycle 1 up to Month 12) and follow-up (Month 18)
Nervous system disorders Headache	11.1% 2/18 • Number of events 2 • Throughout the study, from the baseline to the study termination (from cycle 1 up to Month 12) and follow-up (Month 18)	0.00% 0/7 • Throughout the study, from the baseline to the study termination (from cycle 1 up to Month 12) and follow-up (Month 18)
Nervous system disorders Dizziness	0.00% 0/18 • Throughout the study, from the baseline to the study termination (from cycle 1 up to Month 12) and follow-up (Month 18)	28.6% 2/7 • Number of events 2 • Throughout the study, from the baseline to the study termination (from cycle 1 up to Month 12) and follow-up (Month 18)
Nervous system disorders Parosmia	0.00% 0/18 • Throughout the study, from the baseline to the study termination (from cycle 1 up to Month 12) and follow-up (Month 18)	14.3% 1/7 • Number of events 1 • Throughout the study, from the baseline to the study termination (from cycle 1 up to Month 12) and follow-up (Month 18)
Nervous system disorders Sciatica	0.00% 0/18 • Throughout the study, from the baseline to the study termination (from cycle 1 up to Month 12) and follow-up (Month 18)	14.3% 1/7 • Number of events 1 • Throughout the study, from the baseline to the study termination (from cycle 1 up to Month 12) and follow-up (Month 18)
Nervous system disorders Taste disorders	0.00% 0/18 • Throughout the study, from the baseline to the study termination (from cycle 1 up to Month 12) and follow-up (Month 18)	14.3% 1/7 • Number of events 1 • Throughout the study, from the baseline to the study termination (from cycle 1 up to Month 12) and follow-up (Month 18)
Respiratory, thoracic and mediastinal disorders Dysphonia	5.6% 1/18 • Number of events 1 • Throughout the study, from the baseline to the study termination (from cycle 1 up to Month 12) and follow-up (Month 18)	0.00% 0/7 • Throughout the study, from the baseline to the study termination (from cycle 1 up to Month 12) and follow-up (Month 18)
Respiratory, thoracic and mediastinal disorders Respiratory disorder	5.6% 1/18 • Number of events 1 • Throughout the study, from the baseline to the study termination (from cycle 1 up to Month 12) and follow-up (Month 18)	0.00% 0/7 • Throughout the study, from the baseline to the study termination (from cycle 1 up to Month 12) and follow-up (Month 18)
Respiratory, thoracic and mediastinal disorders Asthma	0.00% 0/18 • Throughout the study, from the baseline to the study termination (from cycle 1 up to Month 12) and follow-up (Month 18)	14.3% 1/7 • Number of events 1 • Throughout the study, from the baseline to the study termination (from cycle 1 up to Month 12) and follow-up (Month 18)
Respiratory, thoracic and mediastinal disorders Nasal congestion	0.00% 0/18 • Throughout the study, from the baseline to the study termination (from cycle 1 up to Month 12) and follow-up (Month 18)	14.3% 1/7 • Number of events 1 • Throughout the study, from the baseline to the study termination (from cycle 1 up to Month 12) and follow-up (Month 18)
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	0.00% 0/18 • Throughout the study, from the baseline to the study termination (from cycle 1 up to Month 12) and follow-up (Month 18)	14.3% 1/7 • Number of events 1 • Throughout the study, from the baseline to the study termination (from cycle 1 up to Month 12) and follow-up (Month 18)
Blood and lymphatic system disorders Normocytic anemia	5.6% 1/18 • Number of events 1 • Throughout the study, from the baseline to the study termination (from cycle 1 up to Month 12) and follow-up (Month 18)	0.00% 0/7 • Throughout the study, from the baseline to the study termination (from cycle 1 up to Month 12) and follow-up (Month 18)
Eye disorders Vision blurred	5.6% 1/18 • Number of events 1 • Throughout the study, from the baseline to the study termination (from cycle 1 up to Month 12) and follow-up (Month 18)	0.00% 0/7 • Throughout the study, from the baseline to the study termination (from cycle 1 up to Month 12) and follow-up (Month 18)
Investigations Occult blood	5.6% 1/18 • Number of events 2 • Throughout the study, from the baseline to the study termination (from cycle 1 up to Month 12) and follow-up (Month 18)	0.00% 0/7 • Throughout the study, from the baseline to the study termination (from cycle 1 up to Month 12) and follow-up (Month 18)
Musculoskeletal and connective tissue disorders Musculoskeletal pain	5.6% 1/18 • Number of events 1 • Throughout the study, from the baseline to the study termination (from cycle 1 up to Month 12) and follow-up (Month 18)	0.00% 0/7 • Throughout the study, from the baseline to the study termination (from cycle 1 up to Month 12) and follow-up (Month 18)
Reproductive system and breast disorders Dysmenorrhea	5.6% 1/18 • Number of events 1 • Throughout the study, from the baseline to the study termination (from cycle 1 up to Month 12) and follow-up (Month 18)	0.00% 0/7 • Throughout the study, from the baseline to the study termination (from cycle 1 up to Month 12) and follow-up (Month 18)
Reproductive system and breast disorders Amenorrhea	0.00% 0/18 • Throughout the study, from the baseline to the study termination (from cycle 1 up to Month 12) and follow-up (Month 18)	14.3% 1/7 • Number of events 1 • Throughout the study, from the baseline to the study termination (from cycle 1 up to Month 12) and follow-up (Month 18)
Reproductive system and breast disorders Vulvovaginal pruritus	0.00% 0/18 • Throughout the study, from the baseline to the study termination (from cycle 1 up to Month 12) and follow-up (Month 18)	14.3% 1/7 • Number of events 2 • Throughout the study, from the baseline to the study termination (from cycle 1 up to Month 12) and follow-up (Month 18)
Skin and subcutaneous tissue disorders Fixed eruption	5.6% 1/18 • Number of events 2 • Throughout the study, from the baseline to the study termination (from cycle 1 up to Month 12) and follow-up (Month 18)	0.00% 0/7 • Throughout the study, from the baseline to the study termination (from cycle 1 up to Month 12) and follow-up (Month 18)
Skin and subcutaneous tissue disorders Erythema	0.00% 0/18 • Throughout the study, from the baseline to the study termination (from cycle 1 up to Month 12) and follow-up (Month 18)	14.3% 1/7 • Number of events 1 • Throughout the study, from the baseline to the study termination (from cycle 1 up to Month 12) and follow-up (Month 18)
Surgical and medical procedures Wisdom teeth removal	5.6% 1/18 • Number of events 2 • Throughout the study, from the baseline to the study termination (from cycle 1 up to Month 12) and follow-up (Month 18)	0.00% 0/7 • Throughout the study, from the baseline to the study termination (from cycle 1 up to Month 12) and follow-up (Month 18)
General disorders Pyrexia	0.00% 0/18 • Throughout the study, from the baseline to the study termination (from cycle 1 up to Month 12) and follow-up (Month 18)	14.3% 1/7 • Number of events 1 • Throughout the study, from the baseline to the study termination (from cycle 1 up to Month 12) and follow-up (Month 18)