A Study in Healthy People to Test Whether Different Doses of BI 1015550 Have Potential to Induce Heart Rhythm Abnormalities

Boehringer Ingelheim

Status and phase: Completed; Phase 1

Conditions: Healthy

Treatments: Drug: BI 1015550; Drug: Moxifloxacin; Drug: Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT06107036

U1111-1295-4664 (Registry Identifier)

1305-0026

Details and patient eligibility

About

The main objective of this trial is to evaluate the effects of a single therapeutic and a single supra-therapeutic dose of BI 1015550 following oral administration on cardiac safety parameters in healthy male and female volunteers.

Enrollment: 46 patients

Sex: All

Ages: 18 to 50 years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

1. Healthy male or female subjects according to the assessment of the investigator, as based on a complete medical history including a physical examination, vital signs - blood pressure (BP) and pulse rate (PR), 12-lead electrocardiogram (ECG), and clinical laboratory tests without any clinically significant abnormalities

2. Age of 18 to 50 years (inclusive)

3. Body mass index of 18.5 to 32 kg/m^2 (inclusive)

4. Signed and dated written informed consent in accordance with International Conference of Harmonization-Good Clinical Practice (ICH-GCP) and local legislation prior to admission to the trial

5. Either male subjects, or female subjects meet the following criteria requiring highly effective contraception from at least 30 days before the first administration of trial medication until 37 days after the last administration of the study drug:

   • Male participants must use condom plus their partner, if identified as a women of childbearing potential (WOCBP), must use an oral contraceptive or highly effective contraception
   • Female participants must be using highly effective contraception and in addition their male partner must use a condom if they are using an oral contraceptive

Exclusion criteria

1. Any finding in the medical examination (including BP, Heart rate (HR) or ECG) deviating from normal and assessed as clinically relevant by the investigator
2. Repeated measurement of systolic blood pressure outside the range of 90 to 140 mmHg, diastolic blood pressure outside the range of 50 to 90 mmHg, or heart rate outside the range of 50 to 90 beats per minute (bpm)
3. Any laboratory value outside the reference range that the investigator considers to be of clinical relevance, in particular, hepatic parameters (alanine transaminase, aspartate transaminase, total bilirubin) or renal parameters (creatinine) exceeding the upper limit of normal
4. Any evidence of a concomitant disease assessed as clinically relevant by the investigator
5. Gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunological or hormonal disorders assessed as clinically relevant by the investigator
6. Cholecystectomy or other surgery of the gastrointestinal tract that could interfere with the pharmacokinetics of the trial medication (except appendectomy or simple hernia repair)
7. Diseases of the central nervous system (including but not limited to any kind of seizures or stroke), and other relevant neurological or psychiatric disorders including but not limited to depression and suicidal behaviour
8. History of clinically relevant orthostatic hypotension, fainting spells, or blackouts Further exclusion criteria apply.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Double Blind

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46 participants in 15 patient groups

Sequence 1: H/M/P2/L/P1

Experimental group

Description:

Participants in this study received five treatments in the order described below. Each treatment was administered orally with 240 mL of water following an overnight fast of at least 10 hours. A washout period of at least 7 days separated each treatment. H (high-dose nerandomilast): Participants received film-coated tablets containing a high dose of nerandomilast. M (high-dose moxifloxacin - Positive Control): Participants received film-coated tablets containing a high dose of moxifloxacin as a positive control. P2 (Placebo 2): Participants received placebo tablets designed to match the high-dose nerandomilast group. L (low-dose nerandomilast): Participants received film-coated tablets containing a low dose of nerandomilast. P1 (Placebo 1): Participants received placebo tablets designed to match the low-dose nerandomilast group.

Treatment:

Drug: Placebo

Drug: Moxifloxacin

Drug: BI 1015550

Sequence 2: H/P1/L/P2/M

Experimental group

Description:

Participants in this study received five treatments in the order described below. Each treatment was administered orally with 240 mL of water following an overnight fast of at least 10 hours. A washout period of at least 7 days separated each treatment. H (high-dose nerandomilast): Participants received film-coated tablets containing a high dose of nerandomilast. P1 (Placebo 1): Participants received placebo tablets designed to match the low-dose nerandomilast group. L (low-dose nerandomilast): Participants received film-coated tablets containing a low dose of nerandomilast. P2 (Placebo 2): Participants received placebo tablets designed to match the high-dose nerandomilast group. M (high-dose moxifloxacin - Positive Control): Participants received film-coated tablets containing a high dose of moxifloxacin as a positive control.

Treatment:

Drug: Placebo

Drug: Moxifloxacin

Drug: BI 1015550

Sequence 3: H/L/P2/M/P1

Experimental group

Description:

Participants in this study received five treatments in the order described below. Each treatment was administered orally with 240 mL of water following an overnight fast of at least 10 hours. A washout period of at least 7 days separated each treatment. H (high-dose nerandomilast): Participants received film-coated tablets containing a high dose of nerandomilast. L (low-dose nerandomilast): Participants received film-coated tablets containing a low dose of nerandomilast. P2 (Placebo 2): Participants received placebo tablets designed to match the high-dose nerandomilast group. M (high-dose moxifloxacin - Positive Control): Participants received film-coated tablets containing a high dose of moxifloxacin as a positive control. P1 (Placebo 1): Participants received placebo tablets designed to match the low-dose nerandomilast group.

Treatment:

Drug: Placebo

Drug: Moxifloxacin

Drug: BI 1015550

Sequence 4: M/H/L/P1/P2

Experimental group

Description:

Participants in this study received five treatments in the order described below. Each treatment was administered orally with 240 mL of water following an overnight fast of at least 10 hours. A washout period of at least 7 days separated each treatment. M (high-dose moxifloxacin - Positive Control): Participants received film-coated tablets containing a high dose of moxifloxacin as a positive control. H (high-dose nerandomilast): Participants received film-coated tablets containing a high dose of nerandomilast. L (low-dose nerandomilast): Participants received film-coated tablets containing a low dose of nerandomilast. P1 (Placebo 1): Participants received placebo tablets designed to match the low-dose nerandomilast group. P2 (Placebo 2): Participants received placebo tablets designed to match the high-dose nerandomilast group.

Treatment:

Drug: Placebo

Drug: Moxifloxacin

Drug: BI 1015550

Sequence 5: M/P1/L/H/P2

Experimental group

Description:

Participants in this study received five treatments in the order described below. Each treatment was administered orally with 240 mL of water following an overnight fast of at least 10 hours. A washout period of at least 7 days separated each treatment. M (high-dose moxifloxacin - Positive Control): Participants received film-coated tablets containing a high dose of moxifloxacin as a positive control. P1 (Placebo 1): Participants received placebo tablets designed to match the low-dose nerandomilast group. L (low-dose nerandomilast): Participants received film-coated tablets containing a low dose of nerandomilast. H (high-dose nerandomilast): Participants received film-coated tablets containing a high dose of nerandomilast. P2 (Placebo 2): Participants received placebo tablets designed to match the high-dose nerandomilast group.

Treatment:

Drug: Placebo

Drug: Moxifloxacin

Drug: BI 1015550

Sequence 6: M/P2/H/L/P1

Experimental group

Description:

Participants in this study received five treatments in the order described below. Each treatment was administered orally with 240 mL of water following an overnight fast of at least 10 hours. A washout period of at least 7 days separated each treatment. M (high-dose moxifloxacin - Positive Control): Participants received film-coated tablets containing a high dose of moxifloxacin as a positive control. P2 (Placebo 2): Participants received placebo tablets designed to match the high-dose nerandomilast group. H (high-dose nerandomilast): Participants received film-coated tablets containing a high dose of nerandomilast. L (low-dose nerandomilast): Participants received film-coated tablets containing a low dose of nerandomilast. P1 (Placebo 1): Participants received placebo tablets designed to match the low-dose nerandomilast group.

Treatment:

Drug: Placebo

Drug: Moxifloxacin

Drug: BI 1015550

Sequence 7: P1/M/H/P2/L

Experimental group

Description:

Participants in this study received five treatments ordered as described below. Each treatment was administered orally with 240 mL of water after an overnight fast of at least 10 hours. Each treatment was separated by a wash-out period of at least 7 days. P1 (Placebo 1): Participants received placebo tablets designed to match the low-dose nerandomilast group. M (high-dose moxifloxacin - Positive Control): Participants received film-coated tablets containing a high dose of moxifloxacin as a positive control. H (high-dose nerandomilast): Participants received film-coated tablets containing a high dose of nerandomilast. P2 (Placebo 2): Participants received placebo tablets designed to match the high-dose nerandomilast group. L (low-dose nerandomilast): Participants received film-coated tablets containing a low dose of nerandomilast.

Treatment:

Drug: Placebo

Drug: Moxifloxacin

Drug: BI 1015550

Sequence 8: P1/P2/H/M/L

Experimental group

Description:

Participants in this study received five treatments in the order described below. Each treatment was administered orally with 240 mL of water following an overnight fast of at least 10 hours. A washout period of at least 7 days separated each treatment. P1 (Placebo 1): Participants received placebo tablets designed to match the low-dose nerandomilast group. P2 (Placebo 2): Participants received placebo tablets designed to match the high-dose nerandomilast group. H (high-dose nerandomilast): Participants received film-coated tablets containing a high dose of nerandomilast. M (high-dose moxifloxacin - Positive Control): Participants received film-coated tablets containing a high dose of moxifloxacin as a positive control. L (low-dose nerandomilast): Participants received film-coated tablets containing a low dose of nerandomilast.

Treatment:

Drug: Placebo

Drug: Moxifloxacin

Drug: BI 1015550

Sequence 9: P1/L/M/H/P2

Experimental group

Description:

Participants in this study received five treatments in the order described below. Each treatment was administered orally with 240 mL of water following an overnight fast of at least 10 hours. A washout period of at least 7 days separated each treatment. P1 (Placebo 1): Participants received placebo tablets designed to match the low-dose nerandomilast group. L (low-dose nerandomilast): Participants received film-coated tablets containing a low dose of nerandomilast. M (high-dose moxifloxacin - Positive Control): Participants received film-coated tablets containing a high dose of moxifloxacin as a positive control. H (high-dose nerandomilast): Participants received film-coated tablets containing a high dose of nerandomilast. P2 (Placebo 2): Participants received placebo tablets designed to match the high-dose nerandomilast group.

Treatment:

Drug: Placebo

Drug: Moxifloxacin

Drug: BI 1015550

Sequence 10: P2/H/P1/M/L

Experimental group

Description:

Participants in this study received five treatments in the order described below. Each treatment was administered orally with 240 mL of water following an overnight fast of at least 10 hours. A washout period of at least 7 days separated each treatment. P2 (Placebo 2): Participants received placebo tablets designed to match the high-dose nerandomilast group. H (high-dose nerandomilast): Participants received film-coated tablets containing a high dose of nerandomilast. P1 (Placebo 1): Participants received placebo tablets designed to match the low-dose nerandomilast group. M (high-dose moxifloxacin - Positive Control): Participants received film-coated tablets containing a high dose of moxifloxacin as a positive control. L (low-dose nerandomilast): Participants received film-coated tablets containing a low dose of nerandomilast.

Treatment:

Drug: Placebo

Drug: Moxifloxacin

Drug: BI 1015550

Sequence 11: P2/P1/M/L/H

Experimental group

Description:

Participants in this study received five treatments ordered as described below. Each treatment was administered orally with 240 mL of water after an overnight fast of at least 10 hours. Each treatment was separated by a wash-out period of at least 7 days. P2 (Placebo 2): Participants received placebo tablets designed to match the high-dose nerandomilast group. P1 (Placebo 1): Participants received placebo tablets designed to match the low-dose nerandomilast group. M (high-dose moxifloxacin - Positive Control): Participants received film-coated tablets containing a high dose of moxifloxacin as a positive control. L (low-dose nerandomilast): Participants received film-coated tablets containing a low dose of nerandomilast. H (high-dose nerandomilast): Participants received film-coated tablets containing a high dose of nerandomilast.

Treatment:

Drug: Placebo

Drug: Moxifloxacin

Drug: BI 1015550

Sequence 12: P2/L/M/P1/H

Experimental group

Description:

Participants in this study received five treatments in the order described below. Each treatment was administered orally with 240 mL of water following an overnight fast of at least 10 hours. A washout period of at least 7 days separated each treatment. P2 (Placebo 2): Participants received placebo tablets designed to match the high-dose nerandomilast group. L (low-dose nerandomilast): Participants received film-coated tablets containing a low dose of nerandomilast. M (high-dose moxifloxacin - Positive Control): Participants received film-coated tablets containing a high dose of moxifloxacin as a positive control. P1 (Placebo 1): Participants received placebo tablets designed to match the low-dose nerandomilast group. H (high-dose nerandomilast): Participants received film-coated tablets containing a high dose of nerandomilast.

Treatment:

Drug: Placebo

Drug: Moxifloxacin

Drug: BI 1015550

Sequence 13: L/H/P1/P2/M

Experimental group

Description:

Participants in this study received five treatments in the order described below. Each treatment was administered orally with 240 mL of water following an overnight fast of at least 10 hours. A washout period of at least 7 days separated each treatment. L (low-dose nerandomilast): Participants received film-coated tablets containing a low dose of nerandomilast. H (high-dose nerandomilast): Participants received film-coated tablets containing a high dose of nerandomilast. P1 (Placebo 1): Participants received placebo tablets designed to match the low-dose nerandomilast group. P2 (Placebo 2): Participants received placebo tablets designed to match the high-dose nerandomilast group. M (high-dose moxifloxacin - Positive Control): Participants received film-coated tablets containing a high dose of moxifloxacin as a positive control.

Treatment:

Drug: Placebo

Drug: Moxifloxacin

Drug: BI 1015550

Sequence 14: L/M/P2/P1/H

Experimental group

Description:

Participants in this study received five treatments ordered as described below. Each treatment was administered orally with 240 mL of water after an overnight fast of at least 10 hours. Each treatment was separated by a wash-out period of at least 7 days. L (low-dose nerandomilast): Participants received film-coated tablets containing a low dose of nerandomilast. M (high-dose moxifloxacin - Positive Control): Participants received film-coated tablets containing a high dose of moxifloxacin as a positive control. P2 (Placebo 2): Participants received placebo tablets designed to match the high-dose nerandomilast group. P1 (Placebo 1): Participants received placebo tablets designed to match the low-dose nerandomilast group. H (high-dose nerandomilast): Participants received film-coated tablets containing a high dose of nerandomilast.

Treatment:

Drug: Placebo

Drug: Moxifloxacin

Drug: BI 1015550

Sequence 15: L/P2/P1/H/M

Experimental group

Description:

Participants in this study received five treatments ordered as described below. Each treatment was administered orally with 240 mL of water after an overnight fast of at least 10 hours. Each treatment was separated by a wash-out period of at least 7 days. L (low-dose nerandomilast): Participants received film-coated tablets containing a low dose of nerandomilast. P2 (Placebo 2): Participants received placebo tablets designed to match the high-dose nerandomilast group. P1 (Placebo 1): Participants received placebo tablets designed to match the low-dose nerandomilast group. H (high-dose nerandomilast): Participants received film-coated tablets containing a high dose of nerandomilast. M (high-dose moxifloxacin - Positive Control): Participants received film-coated tablets containing a high dose of moxifloxacin as a positive control.

Treatment:

Drug: Placebo

Drug: Moxifloxacin

Drug: BI 1015550