Trial Outcomes & Findings for Effect of Clarithromycin on PK of Linaprazan, Linaprazan on PK of Clarithromycin and Linaprazan on PK of Midazolam (NCT NCT05633147)

Last Updated: 2025-01-03

Results Overview

Area under the plasma concentration curve from 0 to infinity (AUC0-inf). The AUC were calculated to the time point of the last quantifiable plasma concentration and then extrapolated to infinity using the concentration in the last quantifiable sample and the estimated terminal elimination rate constant (Lambdaz).

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

35 participants

Primary outcome timeframe

Timepoints collected: pre-dose, 15 min, 30 min, 45 min, 1.15 h, 1.5 h, 2 h, 3 h, 4 h, 6 h, 8 h, 10 h, 12 h, 18 h, 24 h, 36 h, 48 h and 72 h after dosing (on dosing Days 1 and 10).

Results posted on

2025-01-03

Participant Flow

Subjects were recruited from CTC's database of volunteers and from advertising in media (including social media).

Screening details: The screening visits were performed within 28 days prior to dosing (Day 28 to Day -1) for both parts. Part I: 27 subjects were screened and 17 subjects were included in Part I of the study. Part II: 56 subjects were screened and 18 subjects were included in Part II of the study.

Participant milestones

Participant milestones
Measure	Period I, Part I Linaprazan glurate in base form, tablets 100 mg administered under fasting conditions Day 1 and Day 10. Drug drug interaction (DDI) - Clarithromycin (Part I): Index inhibitor (perpetrator drug) Clarithromycin 500 mg twice daily for 9 days (tablets).	Period II, Part II IMP Linaprazan glurate hydrochloride (HCl), tablets 75 mg twice daily for 13 days. Morning dose administered under fasting conditions on Day 2 and Day 14. Drug drug interaction (DDI) - Midazolam: Substrate for CYP3A. Midazolam 2.5 mg once daily (2.5 mL oral solution) Day 1, Day 2 and Day 14.
Overall Study STARTED	17	18
Overall Study COMPLETED	16	18
Overall Study NOT COMPLETED	1	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Effect of Clarithromycin on PK of Linaprazan, Linaprazan on PK of Clarithromycin and Linaprazan on PK of Midazolam

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Part I n=17 Participants Linaprazan glurate in base form, tablets 100 mg administered under fasting conditions Day 1 and Day 10. Drug drug interaction (DDI) - Clarithromycin (Part I): Index inhibitor (perpetrator drug) Clarithromycin 500 mg twice daily for 9 days (tablets).	Part II n=18 Participants IMP Linaprazan glurate hydrochloride (HCl), tablets 75 mg twice daily for 13 days. Morning dose administered under fasting conditions on Day 2 and Day 14. Drug drug interaction (DDI) - Midazolam: Substrate for CYP3A. Midazolam 2.5 mg once daily (2.5 mL oral solution) Day 1, Day 2 and Day 14.	Total n=35 Participants Total of all reporting groups
Age, Continuous	37.5 years STANDARD_DEVIATION 13.0 • n=5 Participants	35.0 years STANDARD_DEVIATION 12.3 • n=7 Participants	36.2 years STANDARD_DEVIATION 12.7 • n=5 Participants
Sex: Female, Male Female	5 Participants n=5 Participants	2 Participants n=7 Participants	7 Participants n=5 Participants
Sex: Female, Male Male	12 Participants n=5 Participants	16 Participants n=7 Participants	28 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	16 Participants n=5 Participants	17 Participants n=7 Participants	33 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Race (NIH/OMB) White	16 Participants n=5 Participants	15 Participants n=7 Participants	31 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Region of Enrollment Sweden	17 participants n=5 Participants	18 participants n=7 Participants	35 participants n=5 Participants

PRIMARY outcome

Timeframe: Timepoints collected: pre-dose, 15 min, 30 min, 45 min, 1.15 h, 1.5 h, 2 h, 3 h, 4 h, 6 h, 8 h, 10 h, 12 h, 18 h, 24 h, 36 h, 48 h and 72 h after dosing (on dosing Days 1 and 10).

Population: Data is presented for: * Linaprazan (active metabolite) after 100 mg single dose administered alone * Linaprazan (active metabolite) after 100 mg single dose co-administered with clarithromycin * Linaprazan glurate (prodrug) after 100 mg single dose administered alone * Linaprazan glurate (prodrug) after 100 mg single dose co-administered with clarithromycin

Outcome measures

Outcome measures
Measure	Part I n=16 Participants Linaprazan glurate in base form, tablets 100 mg administered under fasting conditions Day 1 and Day 10. Drug drug interaction (DDI) - Clarithromycin (Part I): Index inhibitor (perpetrator drug) Clarithromycin 500 mg twice daily for 9 days (tablets).
Period I, Part I - Linaprazan Glurate and Linaprazan PK Parameters With and Without Co-administration of Clarithromycin - AUC0-inf Linaprazan (alone)	13950 h*nmol/L Standard Deviation 5649
Period I, Part I - Linaprazan Glurate and Linaprazan PK Parameters With and Without Co-administration of Clarithromycin - AUC0-inf Linaprazan (co-admin)	42840 h*nmol/L Standard Deviation 16260
Period I, Part I - Linaprazan Glurate and Linaprazan PK Parameters With and Without Co-administration of Clarithromycin - AUC0-inf Linaprazan glurate (alone)	137.3 h*nmol/L Standard Deviation 52.02
Period I, Part I - Linaprazan Glurate and Linaprazan PK Parameters With and Without Co-administration of Clarithromycin - AUC0-inf Linaprazan glurate (co-admin)	165.9 h*nmol/L Standard Deviation 79.56

PRIMARY outcome

Timeframe: Timepoints collected: pre-dose, 15 min, 30 min, 45 min, 1.15 h, 1.5 h, 2 h, 3 h, 4 h, 6 h, 8 h, 10 h, 12 h, 18 h, 24 h, 36 h, 48 h and 72 h after dosing (on dosing Days 1 and 10).

AUC from time 0 to time t (AUC0-t). AUC0-t were analyzed using a mixed model following a natural logarithmic transformation, with fixed effect for treatment and random effect for subject.

Outcome measures

Outcome measures
Measure	Part I n=16 Participants Linaprazan glurate in base form, tablets 100 mg administered under fasting conditions Day 1 and Day 10. Drug drug interaction (DDI) - Clarithromycin (Part I): Index inhibitor (perpetrator drug) Clarithromycin 500 mg twice daily for 9 days (tablets).
Period I, Part I - Linaprazan Glurate and Linaprazan PK Parameters With and Without Co-administration of Clarithromycin - AUC0-t Linaprazan (alone)	13870 h*nmol/L Standard Deviation 5346
Period I, Part I - Linaprazan Glurate and Linaprazan PK Parameters With and Without Co-administration of Clarithromycin - AUC0-t Linaprazan (co-admin)	39870 h*nmol/L Standard Deviation 13840
Period I, Part I - Linaprazan Glurate and Linaprazan PK Parameters With and Without Co-administration of Clarithromycin - AUC0-t Linaprazan glurate (alone)	133.6 h*nmol/L Standard Deviation 51.87
Period I, Part I - Linaprazan Glurate and Linaprazan PK Parameters With and Without Co-administration of Clarithromycin - AUC0-t Linaprazan glurate (co-admin)	160.6 h*nmol/L Standard Deviation 81.64

PRIMARY outcome

Timeframe: and 72 h after dosing (on dosing Days 1 and 10).

Maximum plasma concentration (Cmax). Cmax were analyzed using a mixed model following a natural logarithmic transformation, with fixed effect for treatment and random effect for subject.

Outcome measures

Outcome measures
Measure	Part I n=16 Participants Linaprazan glurate in base form, tablets 100 mg administered under fasting conditions Day 1 and Day 10. Drug drug interaction (DDI) - Clarithromycin (Part I): Index inhibitor (perpetrator drug) Clarithromycin 500 mg twice daily for 9 days (tablets).
Period I, Part I - Linaprazan Glurate and Linaprazan PK Parameters With and Without Co-administration of Clarithromycin - Cmax Linaprazan (alone)	1844 nmol/L Standard Deviation 712.4
Period I, Part I - Linaprazan Glurate and Linaprazan PK Parameters With and Without Co-administration of Clarithromycin - Cmax Linaprazan (co-admin)	2742 nmol/L Standard Deviation 1217
Period I, Part I - Linaprazan Glurate and Linaprazan PK Parameters With and Without Co-administration of Clarithromycin - Cmax Linaprazan glurate (alone)	131.1 nmol/L Standard Deviation 53.72
Period I, Part I - Linaprazan Glurate and Linaprazan PK Parameters With and Without Co-administration of Clarithromycin - Cmax Linaprazan glurate (co-admin)	176.8 nmol/L Standard Deviation 114.3

PRIMARY outcome

Timeframe: Timepoints collected: Pre-dose, 15 min, 30 min, 1 h, 2 h, 4 h, 8 h, 12 h, 14 h, 20 h and 24 h (on day 1, 2 and 14).

Population: Data is presented for: * Midazolam alone, Day 1 * Midazolam co-administered with linaprazan glurate, Day 2 * Midazolam co-administered with linaprazan glurate, Day 14

Area under the plasma concentration curve from 0 to infinity - AUCinf. AUC were calculated to the time point of the last quantifiable plasma concentration and then extrapolated to infinity using the concentration in the last quantifiable sample and the estimated terminal elimination rate constant (Lambdaz).

Outcome measures

Outcome measures
Measure	Part I n=17 Participants Linaprazan glurate in base form, tablets 100 mg administered under fasting conditions Day 1 and Day 10. Drug drug interaction (DDI) - Clarithromycin (Part I): Index inhibitor (perpetrator drug) Clarithromycin 500 mg twice daily for 9 days (tablets).
Period II, Part II- Midazolam PK Parameters in the Presence and Absence of Linaprazan Glurate Administration - AUC0-inf Midazolam (alone)	38.57 h*ng/mL Standard Deviation 13.98
Period II, Part II- Midazolam PK Parameters in the Presence and Absence of Linaprazan Glurate Administration - AUC0-inf Midazolam (co-admin) Day 2	40.78 h*ng/mL Standard Deviation 16.04
Period II, Part II- Midazolam PK Parameters in the Presence and Absence of Linaprazan Glurate Administration - AUC0-inf Midazolam (co-admin) Day 14	33.06 h*ng/mL Standard Deviation 10.46

PRIMARY outcome

Timeframe: Timepoints collected: Pre-dose, 15 min, 30 min, 1 h, 2 h, 4 h, 8 h, 12 h, 14 h, 20 h and 24 h (on day 1, 2 and 14).

Population: Data is presented for: * Midazolam alone, Day 1 * Midazolam co-administered with linaprazan glurate, Day 2 * Midazolam co-administered with linaprazan glurate, Day 14

AUC from time 0 to time t - AUC0-t. AUC0-t were analyzed using a mixed model following a natural logarithmic transformation, with fixed effect for treatment and random effect for subject.

Outcome measures

Outcome measures
Measure	Part I n=17 Participants Linaprazan glurate in base form, tablets 100 mg administered under fasting conditions Day 1 and Day 10. Drug drug interaction (DDI) - Clarithromycin (Part I): Index inhibitor (perpetrator drug) Clarithromycin 500 mg twice daily for 9 days (tablets).
Period II, Part II- Midazolam PK Parameters in the Presence and Absence of Linaprazan Glurate Administration - AUC0-t Midazolam (alone)	37.12 h*ng/mL Standard Deviation 13.86
Period II, Part II- Midazolam PK Parameters in the Presence and Absence of Linaprazan Glurate Administration - AUC0-t Midazolam (co-admin) Day 2	39.66 h*ng/mL Standard Deviation 16.01
Period II, Part II- Midazolam PK Parameters in the Presence and Absence of Linaprazan Glurate Administration - AUC0-t Midazolam (co-admin) Day 14	32.19 h*ng/mL Standard Deviation 10.41

PRIMARY outcome

Timeframe: Timepoints collected: Pre-dose, 15 min, 30 min, 1 h, 2 h, 4 h, 8 h, 12 h, 14 h, 20 h and 24 h (on day 1, 2 and 14).

Population: Data is presented for: * Midazolam alone, Day 1 * Midazolam co-administered with linaprazan glurate, Day 2 * Midazolam co-administered with linaprazan glurate, Day 14

Maximum plasma concentration - Cmax. Cmax were analyzed using a mixed model following a natural logarithmic transformation, with fixed effect for treatment and random effect for subject.

Outcome measures

Outcome measures
Measure	Part I n=17 Participants Linaprazan glurate in base form, tablets 100 mg administered under fasting conditions Day 1 and Day 10. Drug drug interaction (DDI) - Clarithromycin (Part I): Index inhibitor (perpetrator drug) Clarithromycin 500 mg twice daily for 9 days (tablets).
Period II, Part II- Midazolam PK Parameters in the Presence and Absence of Linaprazan Glurate - Cmax Midazolam (alone)	12.24 ng/mL Standard Deviation 4.091
Period II, Part II- Midazolam PK Parameters in the Presence and Absence of Linaprazan Glurate - Cmax Midazolam (co-admin) Day 2	13.69 ng/mL Standard Deviation 5.892
Period II, Part II- Midazolam PK Parameters in the Presence and Absence of Linaprazan Glurate - Cmax Midazolam (co-admin) Day 14	13.53 ng/mL Standard Deviation 6.092

Adverse Events

Part I

Serious events: 0 serious events

Other events: 11 other events

Deaths: 0 deaths

Part II

Serious events: 0 serious events

Other events: 8 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Additional Information

Kajsa Larsson, CMO

Cinclus Pharma Holding AB

Phone: +46 706750128

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Other adverse events
Measure	Part I n=17 participants at risk Linaprazan glurate in base form, tablets 100 mg administered under fasting conditions Day 1 and Day 10. Drug drug interaction (DDI) - Clarithromycin (Part I): Index inhibitor (perpetrator drug) Clarithromycin 500 mg twice daily for 9 days (tablets).	Part II n=18 participants at risk IMP Linaprazan glurate hydrochloride (HCl), tablets 75 mg twice daily for 13 days. Morning dose administered under fasting conditions on Day 2 and Day 14. Drug drug interaction (DDI) - Midazolam: Substrate for CYP3A. Midazolam 2.5 mg once daily (2.5 mL oral solution) Day 1, Day 2 and Day 14.
Injury, poisoning and procedural complications Muscle contusion	5.9% 1/17 • Number of events 1 • Period I, Part I: AEs (including SAEs) were collected from start of IMP administration (Day 1) until the end-of-study visit on Day 14. Period II, Part II: AEs (including SAEs) were collected from start of IMP administration (Day 1) until the end-of-study visit on Day 22. The grading of the severity/intensity (grade 1 to grade 5) of AEs followed the common terminology criteria for AEs (CTCAE) v5.0. AEs were assessed as unlikely, possibly, or probably related to the IMPs.	0.00% 0/18 • Period I, Part I: AEs (including SAEs) were collected from start of IMP administration (Day 1) until the end-of-study visit on Day 14. Period II, Part II: AEs (including SAEs) were collected from start of IMP administration (Day 1) until the end-of-study visit on Day 22. The grading of the severity/intensity (grade 1 to grade 5) of AEs followed the common terminology criteria for AEs (CTCAE) v5.0. AEs were assessed as unlikely, possibly, or probably related to the IMPs.
Nervous system disorders Dysgeusia	11.8% 2/17 • Number of events 2 • Period I, Part I: AEs (including SAEs) were collected from start of IMP administration (Day 1) until the end-of-study visit on Day 14. Period II, Part II: AEs (including SAEs) were collected from start of IMP administration (Day 1) until the end-of-study visit on Day 22. The grading of the severity/intensity (grade 1 to grade 5) of AEs followed the common terminology criteria for AEs (CTCAE) v5.0. AEs were assessed as unlikely, possibly, or probably related to the IMPs.	0.00% 0/18 • Period I, Part I: AEs (including SAEs) were collected from start of IMP administration (Day 1) until the end-of-study visit on Day 14. Period II, Part II: AEs (including SAEs) were collected from start of IMP administration (Day 1) until the end-of-study visit on Day 22. The grading of the severity/intensity (grade 1 to grade 5) of AEs followed the common terminology criteria for AEs (CTCAE) v5.0. AEs were assessed as unlikely, possibly, or probably related to the IMPs.
Nervous system disorders Headache	17.6% 3/17 • Number of events 3 • Period I, Part I: AEs (including SAEs) were collected from start of IMP administration (Day 1) until the end-of-study visit on Day 14. Period II, Part II: AEs (including SAEs) were collected from start of IMP administration (Day 1) until the end-of-study visit on Day 22. The grading of the severity/intensity (grade 1 to grade 5) of AEs followed the common terminology criteria for AEs (CTCAE) v5.0. AEs were assessed as unlikely, possibly, or probably related to the IMPs.	11.1% 2/18 • Number of events 2 • Period I, Part I: AEs (including SAEs) were collected from start of IMP administration (Day 1) until the end-of-study visit on Day 14. Period II, Part II: AEs (including SAEs) were collected from start of IMP administration (Day 1) until the end-of-study visit on Day 22. The grading of the severity/intensity (grade 1 to grade 5) of AEs followed the common terminology criteria for AEs (CTCAE) v5.0. AEs were assessed as unlikely, possibly, or probably related to the IMPs.
General disorders Fatigue	11.8% 2/17 • Number of events 2 • Period I, Part I: AEs (including SAEs) were collected from start of IMP administration (Day 1) until the end-of-study visit on Day 14. Period II, Part II: AEs (including SAEs) were collected from start of IMP administration (Day 1) until the end-of-study visit on Day 22. The grading of the severity/intensity (grade 1 to grade 5) of AEs followed the common terminology criteria for AEs (CTCAE) v5.0. AEs were assessed as unlikely, possibly, or probably related to the IMPs.	0.00% 0/18 • Period I, Part I: AEs (including SAEs) were collected from start of IMP administration (Day 1) until the end-of-study visit on Day 14. Period II, Part II: AEs (including SAEs) were collected from start of IMP administration (Day 1) until the end-of-study visit on Day 22. The grading of the severity/intensity (grade 1 to grade 5) of AEs followed the common terminology criteria for AEs (CTCAE) v5.0. AEs were assessed as unlikely, possibly, or probably related to the IMPs.
General disorders Malaise	5.9% 1/17 • Number of events 1 • Period I, Part I: AEs (including SAEs) were collected from start of IMP administration (Day 1) until the end-of-study visit on Day 14. Period II, Part II: AEs (including SAEs) were collected from start of IMP administration (Day 1) until the end-of-study visit on Day 22. The grading of the severity/intensity (grade 1 to grade 5) of AEs followed the common terminology criteria for AEs (CTCAE) v5.0. AEs were assessed as unlikely, possibly, or probably related to the IMPs.	0.00% 0/18 • Period I, Part I: AEs (including SAEs) were collected from start of IMP administration (Day 1) until the end-of-study visit on Day 14. Period II, Part II: AEs (including SAEs) were collected from start of IMP administration (Day 1) until the end-of-study visit on Day 22. The grading of the severity/intensity (grade 1 to grade 5) of AEs followed the common terminology criteria for AEs (CTCAE) v5.0. AEs were assessed as unlikely, possibly, or probably related to the IMPs.
General disorders Vessel puncture site bruise	0.00% 0/17 • Period I, Part I: AEs (including SAEs) were collected from start of IMP administration (Day 1) until the end-of-study visit on Day 14. Period II, Part II: AEs (including SAEs) were collected from start of IMP administration (Day 1) until the end-of-study visit on Day 22. The grading of the severity/intensity (grade 1 to grade 5) of AEs followed the common terminology criteria for AEs (CTCAE) v5.0. AEs were assessed as unlikely, possibly, or probably related to the IMPs.	5.6% 1/18 • Number of events 1 • Period I, Part I: AEs (including SAEs) were collected from start of IMP administration (Day 1) until the end-of-study visit on Day 14. Period II, Part II: AEs (including SAEs) were collected from start of IMP administration (Day 1) until the end-of-study visit on Day 22. The grading of the severity/intensity (grade 1 to grade 5) of AEs followed the common terminology criteria for AEs (CTCAE) v5.0. AEs were assessed as unlikely, possibly, or probably related to the IMPs.
Gastrointestinal disorders Abdominal pain upper	5.9% 1/17 • Number of events 2 • Period I, Part I: AEs (including SAEs) were collected from start of IMP administration (Day 1) until the end-of-study visit on Day 14. Period II, Part II: AEs (including SAEs) were collected from start of IMP administration (Day 1) until the end-of-study visit on Day 22. The grading of the severity/intensity (grade 1 to grade 5) of AEs followed the common terminology criteria for AEs (CTCAE) v5.0. AEs were assessed as unlikely, possibly, or probably related to the IMPs.	5.6% 1/18 • Number of events 1 • Period I, Part I: AEs (including SAEs) were collected from start of IMP administration (Day 1) until the end-of-study visit on Day 14. Period II, Part II: AEs (including SAEs) were collected from start of IMP administration (Day 1) until the end-of-study visit on Day 22. The grading of the severity/intensity (grade 1 to grade 5) of AEs followed the common terminology criteria for AEs (CTCAE) v5.0. AEs were assessed as unlikely, possibly, or probably related to the IMPs.
Gastrointestinal disorders Abdominal pain	0.00% 0/17 • Period I, Part I: AEs (including SAEs) were collected from start of IMP administration (Day 1) until the end-of-study visit on Day 14. Period II, Part II: AEs (including SAEs) were collected from start of IMP administration (Day 1) until the end-of-study visit on Day 22. The grading of the severity/intensity (grade 1 to grade 5) of AEs followed the common terminology criteria for AEs (CTCAE) v5.0. AEs were assessed as unlikely, possibly, or probably related to the IMPs.	5.6% 1/18 • Number of events 1 • Period I, Part I: AEs (including SAEs) were collected from start of IMP administration (Day 1) until the end-of-study visit on Day 14. Period II, Part II: AEs (including SAEs) were collected from start of IMP administration (Day 1) until the end-of-study visit on Day 22. The grading of the severity/intensity (grade 1 to grade 5) of AEs followed the common terminology criteria for AEs (CTCAE) v5.0. AEs were assessed as unlikely, possibly, or probably related to the IMPs.
Gastrointestinal disorders Nausea	0.00% 0/17 • Period I, Part I: AEs (including SAEs) were collected from start of IMP administration (Day 1) until the end-of-study visit on Day 14. Period II, Part II: AEs (including SAEs) were collected from start of IMP administration (Day 1) until the end-of-study visit on Day 22. The grading of the severity/intensity (grade 1 to grade 5) of AEs followed the common terminology criteria for AEs (CTCAE) v5.0. AEs were assessed as unlikely, possibly, or probably related to the IMPs.	5.6% 1/18 • Number of events 1 • Period I, Part I: AEs (including SAEs) were collected from start of IMP administration (Day 1) until the end-of-study visit on Day 14. Period II, Part II: AEs (including SAEs) were collected from start of IMP administration (Day 1) until the end-of-study visit on Day 22. The grading of the severity/intensity (grade 1 to grade 5) of AEs followed the common terminology criteria for AEs (CTCAE) v5.0. AEs were assessed as unlikely, possibly, or probably related to the IMPs.
Gastrointestinal disorders Anal fissure	5.9% 1/17 • Number of events 1 • Period I, Part I: AEs (including SAEs) were collected from start of IMP administration (Day 1) until the end-of-study visit on Day 14. Period II, Part II: AEs (including SAEs) were collected from start of IMP administration (Day 1) until the end-of-study visit on Day 22. The grading of the severity/intensity (grade 1 to grade 5) of AEs followed the common terminology criteria for AEs (CTCAE) v5.0. AEs were assessed as unlikely, possibly, or probably related to the IMPs.	0.00% 0/18 • Period I, Part I: AEs (including SAEs) were collected from start of IMP administration (Day 1) until the end-of-study visit on Day 14. Period II, Part II: AEs (including SAEs) were collected from start of IMP administration (Day 1) until the end-of-study visit on Day 22. The grading of the severity/intensity (grade 1 to grade 5) of AEs followed the common terminology criteria for AEs (CTCAE) v5.0. AEs were assessed as unlikely, possibly, or probably related to the IMPs.
Gastrointestinal disorders Diarrhoea	11.8% 2/17 • Number of events 2 • Period I, Part I: AEs (including SAEs) were collected from start of IMP administration (Day 1) until the end-of-study visit on Day 14. Period II, Part II: AEs (including SAEs) were collected from start of IMP administration (Day 1) until the end-of-study visit on Day 22. The grading of the severity/intensity (grade 1 to grade 5) of AEs followed the common terminology criteria for AEs (CTCAE) v5.0. AEs were assessed as unlikely, possibly, or probably related to the IMPs.	0.00% 0/18 • Period I, Part I: AEs (including SAEs) were collected from start of IMP administration (Day 1) until the end-of-study visit on Day 14. Period II, Part II: AEs (including SAEs) were collected from start of IMP administration (Day 1) until the end-of-study visit on Day 22. The grading of the severity/intensity (grade 1 to grade 5) of AEs followed the common terminology criteria for AEs (CTCAE) v5.0. AEs were assessed as unlikely, possibly, or probably related to the IMPs.
Gastrointestinal disorders Faeces soft	5.9% 1/17 • Number of events 1 • Period I, Part I: AEs (including SAEs) were collected from start of IMP administration (Day 1) until the end-of-study visit on Day 14. Period II, Part II: AEs (including SAEs) were collected from start of IMP administration (Day 1) until the end-of-study visit on Day 22. The grading of the severity/intensity (grade 1 to grade 5) of AEs followed the common terminology criteria for AEs (CTCAE) v5.0. AEs were assessed as unlikely, possibly, or probably related to the IMPs.	0.00% 0/18 • Period I, Part I: AEs (including SAEs) were collected from start of IMP administration (Day 1) until the end-of-study visit on Day 14. Period II, Part II: AEs (including SAEs) were collected from start of IMP administration (Day 1) until the end-of-study visit on Day 22. The grading of the severity/intensity (grade 1 to grade 5) of AEs followed the common terminology criteria for AEs (CTCAE) v5.0. AEs were assessed as unlikely, possibly, or probably related to the IMPs.
Gastrointestinal disorders Flatulence	5.9% 1/17 • Number of events 1 • Period I, Part I: AEs (including SAEs) were collected from start of IMP administration (Day 1) until the end-of-study visit on Day 14. Period II, Part II: AEs (including SAEs) were collected from start of IMP administration (Day 1) until the end-of-study visit on Day 22. The grading of the severity/intensity (grade 1 to grade 5) of AEs followed the common terminology criteria for AEs (CTCAE) v5.0. AEs were assessed as unlikely, possibly, or probably related to the IMPs.	0.00% 0/18 • Period I, Part I: AEs (including SAEs) were collected from start of IMP administration (Day 1) until the end-of-study visit on Day 14. Period II, Part II: AEs (including SAEs) were collected from start of IMP administration (Day 1) until the end-of-study visit on Day 22. The grading of the severity/intensity (grade 1 to grade 5) of AEs followed the common terminology criteria for AEs (CTCAE) v5.0. AEs were assessed as unlikely, possibly, or probably related to the IMPs.
Gastrointestinal disorders Vomiting	5.9% 1/17 • Number of events 1 • Period I, Part I: AEs (including SAEs) were collected from start of IMP administration (Day 1) until the end-of-study visit on Day 14. Period II, Part II: AEs (including SAEs) were collected from start of IMP administration (Day 1) until the end-of-study visit on Day 22. The grading of the severity/intensity (grade 1 to grade 5) of AEs followed the common terminology criteria for AEs (CTCAE) v5.0. AEs were assessed as unlikely, possibly, or probably related to the IMPs.	0.00% 0/18 • Period I, Part I: AEs (including SAEs) were collected from start of IMP administration (Day 1) until the end-of-study visit on Day 14. Period II, Part II: AEs (including SAEs) were collected from start of IMP administration (Day 1) until the end-of-study visit on Day 22. The grading of the severity/intensity (grade 1 to grade 5) of AEs followed the common terminology criteria for AEs (CTCAE) v5.0. AEs were assessed as unlikely, possibly, or probably related to the IMPs.
Respiratory, thoracic and mediastinal disorders Epistaxis	0.00% 0/17 • Period I, Part I: AEs (including SAEs) were collected from start of IMP administration (Day 1) until the end-of-study visit on Day 14. Period II, Part II: AEs (including SAEs) were collected from start of IMP administration (Day 1) until the end-of-study visit on Day 22. The grading of the severity/intensity (grade 1 to grade 5) of AEs followed the common terminology criteria for AEs (CTCAE) v5.0. AEs were assessed as unlikely, possibly, or probably related to the IMPs.	5.6% 1/18 • Number of events 1 • Period I, Part I: AEs (including SAEs) were collected from start of IMP administration (Day 1) until the end-of-study visit on Day 14. Period II, Part II: AEs (including SAEs) were collected from start of IMP administration (Day 1) until the end-of-study visit on Day 22. The grading of the severity/intensity (grade 1 to grade 5) of AEs followed the common terminology criteria for AEs (CTCAE) v5.0. AEs were assessed as unlikely, possibly, or probably related to the IMPs.
Respiratory, thoracic and mediastinal disorders Rhinorrhoea	0.00% 0/17 • Period I, Part I: AEs (including SAEs) were collected from start of IMP administration (Day 1) until the end-of-study visit on Day 14. Period II, Part II: AEs (including SAEs) were collected from start of IMP administration (Day 1) until the end-of-study visit on Day 22. The grading of the severity/intensity (grade 1 to grade 5) of AEs followed the common terminology criteria for AEs (CTCAE) v5.0. AEs were assessed as unlikely, possibly, or probably related to the IMPs.	5.6% 1/18 • Number of events 1 • Period I, Part I: AEs (including SAEs) were collected from start of IMP administration (Day 1) until the end-of-study visit on Day 14. Period II, Part II: AEs (including SAEs) were collected from start of IMP administration (Day 1) until the end-of-study visit on Day 22. The grading of the severity/intensity (grade 1 to grade 5) of AEs followed the common terminology criteria for AEs (CTCAE) v5.0. AEs were assessed as unlikely, possibly, or probably related to the IMPs.
Respiratory, thoracic and mediastinal disorders Cough	5.9% 1/17 • Number of events 1 • Period I, Part I: AEs (including SAEs) were collected from start of IMP administration (Day 1) until the end-of-study visit on Day 14. Period II, Part II: AEs (including SAEs) were collected from start of IMP administration (Day 1) until the end-of-study visit on Day 22. The grading of the severity/intensity (grade 1 to grade 5) of AEs followed the common terminology criteria for AEs (CTCAE) v5.0. AEs were assessed as unlikely, possibly, or probably related to the IMPs.	0.00% 0/18 • Period I, Part I: AEs (including SAEs) were collected from start of IMP administration (Day 1) until the end-of-study visit on Day 14. Period II, Part II: AEs (including SAEs) were collected from start of IMP administration (Day 1) until the end-of-study visit on Day 22. The grading of the severity/intensity (grade 1 to grade 5) of AEs followed the common terminology criteria for AEs (CTCAE) v5.0. AEs were assessed as unlikely, possibly, or probably related to the IMPs.
Skin and subcutaneous tissue disorders Erythema	11.8% 2/17 • Number of events 2 • Period I, Part I: AEs (including SAEs) were collected from start of IMP administration (Day 1) until the end-of-study visit on Day 14. Period II, Part II: AEs (including SAEs) were collected from start of IMP administration (Day 1) until the end-of-study visit on Day 22. The grading of the severity/intensity (grade 1 to grade 5) of AEs followed the common terminology criteria for AEs (CTCAE) v5.0. AEs were assessed as unlikely, possibly, or probably related to the IMPs.	0.00% 0/18 • Period I, Part I: AEs (including SAEs) were collected from start of IMP administration (Day 1) until the end-of-study visit on Day 14. Period II, Part II: AEs (including SAEs) were collected from start of IMP administration (Day 1) until the end-of-study visit on Day 22. The grading of the severity/intensity (grade 1 to grade 5) of AEs followed the common terminology criteria for AEs (CTCAE) v5.0. AEs were assessed as unlikely, possibly, or probably related to the IMPs.
Psychiatric disorders Nightmare	0.00% 0/17 • Period I, Part I: AEs (including SAEs) were collected from start of IMP administration (Day 1) until the end-of-study visit on Day 14. Period II, Part II: AEs (including SAEs) were collected from start of IMP administration (Day 1) until the end-of-study visit on Day 22. The grading of the severity/intensity (grade 1 to grade 5) of AEs followed the common terminology criteria for AEs (CTCAE) v5.0. AEs were assessed as unlikely, possibly, or probably related to the IMPs.	5.6% 1/18 • Number of events 1 • Period I, Part I: AEs (including SAEs) were collected from start of IMP administration (Day 1) until the end-of-study visit on Day 14. Period II, Part II: AEs (including SAEs) were collected from start of IMP administration (Day 1) until the end-of-study visit on Day 22. The grading of the severity/intensity (grade 1 to grade 5) of AEs followed the common terminology criteria for AEs (CTCAE) v5.0. AEs were assessed as unlikely, possibly, or probably related to the IMPs.
Infections and infestations Nasopharyngitis	5.9% 1/17 • Number of events 1 • Period I, Part I: AEs (including SAEs) were collected from start of IMP administration (Day 1) until the end-of-study visit on Day 14. Period II, Part II: AEs (including SAEs) were collected from start of IMP administration (Day 1) until the end-of-study visit on Day 22. The grading of the severity/intensity (grade 1 to grade 5) of AEs followed the common terminology criteria for AEs (CTCAE) v5.0. AEs were assessed as unlikely, possibly, or probably related to the IMPs.	5.6% 1/18 • Number of events 1 • Period I, Part I: AEs (including SAEs) were collected from start of IMP administration (Day 1) until the end-of-study visit on Day 14. Period II, Part II: AEs (including SAEs) were collected from start of IMP administration (Day 1) until the end-of-study visit on Day 22. The grading of the severity/intensity (grade 1 to grade 5) of AEs followed the common terminology criteria for AEs (CTCAE) v5.0. AEs were assessed as unlikely, possibly, or probably related to the IMPs.