This Study in Healthy Men and Women Tests Whether BI 409306 Has an Effect on the ECG (Thorough QT Study)

Boehringer Ingelheim

Status and phase: Completed; Phase 1

Conditions: Healthy

Treatments: Drug: Moxifloxacin; Drug: Placebo matching to BI 409306; Drug: BI 409306

Study type: Interventional

Funder types: Industry

Identifiers

NCT03934203

1289-0038

2018-001335-44 (EudraCT Number)

Details and patient eligibility

About

The primary objective of this trial is to assess the effect of BI 409306 on the QT/QTc interval in healthy male and female volunteers as measured by the QTcF change from baseline compared with placebo.

Secondary objectives are to show the assay sensitivity of the trial, by reproducing the typical effect of the positive control moxifloxacin on the QT/QTc interval, and to assess the effect of BI 409306 on heart rate.

Enrollment: 47 patients

Sex: All

Ages: 18 to 50 years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

• Healthy male or female subjects according to the assessment of the investigator, based on a complete medical history including a physical examination, vital signs (Blood Pressure (BP), Pulse Rate (PR)), 12-lead single Electrocardiogram (ECG) and 12-lead Holter Electrocardiogram (ECG), and clinical laboratory tests

• Age of 18 to 50 years (incl.)

• Body mass index (BMI) of 18.5 to 29.9 kg/m2 (incl.)

• Signed and dated written informed consent prior to admission to the study in accordance with Good clinical practice (GCP) and local legislation

• Male subjects, or female subjects who meet any of the following criteria starting from at least 30 days before the first administration of trial medication and until 30 days after trial completion:

  • Use of adequate contraception, e.g. non-hormonal intrauterine device plus condom
  • Sexually abstinent
  • A vasectomised sexual partner (vasectomy at least 1 year prior to enrolment)
  • Surgically sterilised (including hysterectomy)
  • Postmenopausal, defined as at least 1 year of spontaneous amenorrhea (in questionable cases a blood sample with simultaneous levels of FSH above 40 U/L and estradiol below 30 ng/L is confirmatory)

Exclusion criteria

• Any finding in the medical examination (including Blood Pressure (BP), Pulse Rate (PR) or Electrocardiogram (ECG)) is deviating from normal and judged as clinically relevant by the investigator
• Repeated measurement of systolic blood pressure outside the range of 100 to 140 mmHg, diastolic blood pressure outside the range of 50 to 90 mmHg, or pulse rate outside the range of 45 to 90 bpm
• Any laboratory value outside the reference range that the investigator considers to be of clinical relevance
• Any evidence of a concomitant disease judged as clinically relevant by the investigator
• Gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunological or hormonal disorders
• Cholecystectomy and/or surgery of the gastrointestinal tract that could interfere with the pharmacokinetics of the trial medication (except appendectomy and simple hernia repair)
• Diseases of the central nervous system (including but not limited to any kind of seizures or stroke), and other relevant neurological or psychiatric disorders
• History of relevant orthostatic hypotension, fainting spells, or blackouts
• Chronic or relevant acute infections
• History of relevant allergy or hypersensitivity (including allergy to the trial medication or its excipients)
• Further exclusion criteria apply

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Double Blind

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47 participants in 15 patient groups

H/L/P/P/M treatment sequence

Experimental group

Description:

In this randomized, placebo-controlled, 5-period crossover trial participants were randomized to one of 15 possible treatment sequences based on a balanced, Prescott triple Latin square design. Treatments administered were 50 mg BI 409306 administered orally as a single dose (1 film-coated tablet plus 4 film-coated placebo tablets), 250 mg BI 409306 administered orally as a single dose (5 film-coated tablets), 400 mg moxifloxacin administered orally as a single dose (1 film-coated tablet), Placebo 1 and Placebo 2 both administered orally as a single dose (5 film-coated tablets). In all treatment periods tablets were taken with 240 milliliter of water after an overnight fast of at least 10 hours on day 1 of the treatment period. The trial was double-blind for placebo and BI 409306, but open-label for moxifloxacin. A washout period of least 6 days was adhered to between drug administrations. L=50 mg BI 409306, H=250 mg BI 409306, M= 400 mg moxifloxacin, P=Placebo 1/Placebo 2.

Treatment:

Drug: Placebo matching to BI 409306

Drug: BI 409306

Drug: Moxifloxacin

H/M/P/P/L treatment sequence

Experimental group

Description:

In this randomized, placebo-controlled, 5-period crossover trial participants were randomized to one of 15 possible treatment sequences based on a balanced, Prescott triple Latin square design. Treatments administered were 50 mg BI 409306 administered orally as a single dose (1 film-coated tablet plus 4 film-coated placebo tablets), 250 mg BI 409306 administered orally as a single dose (5 film-coated tablets), 400 mg moxifloxacin administered orally as a single dose (1 film-coated tablet), Placebo 1 and Placebo 2 both administered orally as a single dose (5 film-coated tablets). In all treatment periods tablets were taken with 240 milliliter of water after an overnight fast of at least 10 hours on day 1 of the treatment period. The trial was double-blind for placebo and BI 409306, but open-label for moxifloxacin. A washout period of least 6 days was adhered to between drug administrations. L=50 mg BI 409306, H=250 mg BI 409306, M= 400 mg moxifloxacin, P=Placebo 1/Placebo 2.

Treatment:

Drug: Placebo matching to BI 409306

Drug: BI 409306

Drug: Moxifloxacin

H/P/P/M/L treatment sequence

Experimental group

Description:

In this randomized, placebo-controlled, 5-period crossover trial participants were randomized to one of 15 possible treatment sequences based on a balanced, Prescott triple Latin square design. Treatments administered were 50 mg BI 409306 administered orally as a single dose (1 film-coated tablet plus 4 film-coated placebo tablets), 250 mg BI 409306 administered orally as a single dose (5 film-coated tablets), 400 mg moxifloxacin administered orally as a single dose (1 film-coated tablet), Placebo 1 and Placebo 2 both administered orally as a single dose (5 film-coated tablets). In all treatment periods tablets were taken with 240 milliliter of water after an overnight fast of at least 10 hours on day 1 of the treatment period. The trial was double-blind for placebo and BI 409306, but open-label for moxifloxacin. A washout period of least 6 days was adhered to between drug administrations. L=50 mg BI 409306, H=250 mg BI 409306, M= 400 mg moxifloxacin, P=Placebo 1/Placebo 2.

Treatment:

Drug: Placebo matching to BI 409306

Drug: BI 409306

Drug: Moxifloxacin

L/M/H/P/P treatment sequence

Experimental group

Description:

In this randomized, placebo-controlled, 5-period crossover trial participants were randomized to one of 15 possible treatment sequences based on a balanced, Prescott triple Latin square design. Treatments administered were 50 mg BI 409306 administered orally as a single dose (1 film-coated tablet plus 4 film-coated placebo tablets), 250 mg BI 409306 administered orally as a single dose (5 film-coated tablets), 400 mg moxifloxacin administered orally as a single dose (1 film-coated tablet), Placebo 1 and Placebo 2 both administered orally as a single dose (5 film-coated tablets). In all treatment periods tablets were taken with 240 milliliter of water after an overnight fast of at least 10 hours on day 1 of the treatment period. The trial was double-blind for placebo and BI 409306, but open-label for moxifloxacin. A washout period of least 6 days was adhered to between drug administrations. L=50 mg BI 409306, H=250 mg BI 409306, M= 400 mg moxifloxacin, P=Placebo 1/Placebo 2.

Treatment:

Drug: Placebo matching to BI 409306

Drug: BI 409306

Drug: Moxifloxacin

L/P/H/M/P treatment sequence

Experimental group

Description:

In this randomized, placebo-controlled, 5-period crossover trial participants were randomized to one of 15 possible treatment sequences based on a balanced, Prescott triple Latin square design. Treatments administered were 50 mg BI 409306 administered orally as a single dose (1 film-coated tablet plus 4 film-coated placebo tablets), 250 mg BI 409306 administered orally as a single dose (5 film-coated tablets), 400 mg moxifloxacin administered orally as a single dose (1 film-coated tablet), Placebo 1 and Placebo 2 both administered orally as a single dose (5 film-coated tablets). In all treatment periods tablets were taken with 240 milliliter of water after an overnight fast of at least 10 hours on day 1 of the treatment period. The trial was double-blind for placebo and BI 409306, but open-label for moxifloxacin. A washout period of least 6 days was adhered to between drug administrations. L=50 mg BI 409306, H=250 mg BI 409306, M= 400 mg moxifloxacin, P=Placebo 1/Placebo 2.

Treatment:

Drug: Placebo matching to BI 409306

Drug: BI 409306

Drug: Moxifloxacin

L/P/M/H/P treatment sequence

Experimental group

Description:

In this randomized, placebo-controlled, 5-period crossover trial participants were randomized to one of 15 possible treatment sequences based on a balanced, Prescott triple Latin square design. Treatments administered were 50 mg BI 409306 administered orally as a single dose (1 film-coated tablet plus 4 film-coated placebo tablets), 250 mg BI 409306 administered orally as a single dose (5 film-coated tablets), 400 mg moxifloxacin administered orally as a single dose (1 film-coated tablet), Placebo 1 and Placebo 2 both administered orally as a single dose (5 film-coated tablets). In all treatment periods tablets were taken with 240 milliliter of water after an overnight fast of at least 10 hours on day 1 of the treatment period. The trial was double-blind for placebo and BI 409306, but open-label for moxifloxacin. A washout period of least 6 days was adhered to between drug administrations. L=50 mg BI 409306, H=250 mg BI 409306, M= 400 mg moxifloxacin, P=Placebo 1/Placebo 2.

Treatment:

Drug: Placebo matching to BI 409306

Drug: BI 409306

Drug: Moxifloxacin

M/H/P/L/P treatment sequence

Experimental group

Description:

In this randomized, placebo-controlled, 5-period crossover trial participants were randomized to one of 15 possible treatment sequences based on a balanced, Prescott triple Latin square design. Treatments administered were 50 mg BI 409306 administered orally as a single dose (1 film-coated tablet plus 4 film-coated placebo tablets), 250 mg BI 409306 administered orally as a single dose (5 film-coated tablets), 400 mg moxifloxacin administered orally as a single dose (1 film-coated tablet), Placebo 1 and Placebo 2 both administered orally as a single dose (5 film-coated tablets). In all treatment periods tablets were taken with 240 milliliter of water after an overnight fast of at least 10 hours on day 1 of the treatment period. The trial was double-blind for placebo and BI 409306, but open-label for moxifloxacin. A washout period of least 6 days was adhered to between drug administrations. L=50 mg BI 409306, H=250 mg BI 409306, M= 400 mg moxifloxacin, P=Placebo 1/Placebo 2.

Treatment:

Drug: Placebo matching to BI 409306

Drug: BI 409306

Drug: Moxifloxacin

M/L/P/H/P treatment sequence

Experimental group

Description:

In this randomized, placebo-controlled, 5-period crossover trial participants were randomized to one of 15 possible treatment sequences based on a balanced, Prescott triple Latin square design. Treatments administered were 50 mg BI 409306 administered orally as a single dose (1 film-coated tablet plus 4 film-coated placebo tablets), 250 mg BI 409306 administered orally as a single dose (5 film-coated tablets), 400 mg moxifloxacin administered orally as a single dose (1 film-coated tablet), Placebo 1 and Placebo 2 both administered orally as a single dose (5 film-coated tablets). In all treatment periods tablets were taken with 240 milliliter of water after an overnight fast of at least 10 hours on day 1 of the treatment period. The trial was double-blind for placebo and BI 409306, but open-label for moxifloxacin. A washout period of least 6 days was adhered to between drug administrations. L=50 mg BI 409306, H=250 mg BI 409306, M= 400 mg moxifloxacin, P=Placebo 1/Placebo 2.

Treatment:

Drug: Placebo matching to BI 409306

Drug: BI 409306

Drug: Moxifloxacin

M/P/H/P/L treatment sequence

Experimental group

Description:

In this randomized, placebo-controlled, 5-period crossover trial participants were randomized to one of 15 possible treatment sequences based on a balanced, Prescott triple Latin square design. Treatments administered were 50 mg BI 409306 administered orally as a single dose (1 film-coated tablet plus 4 film-coated placebo tablets), 250 mg BI 409306 administered orally as a single dose (5 film-coated tablets), 400 mg moxifloxacin administered orally as a single dose (1 film-coated tablet), Placebo 1 and Placebo 2 both administered orally as a single dose (5 film-coated tablets). In all treatment periods tablets were taken with 240 milliliter of water after an overnight fast of at least 10 hours on day 1 of the treatment period. The trial was double-blind for placebo and BI 409306, but open-label for moxifloxacin. A washout period of least 6 days was adhered to between drug administrations. L=50 mg BI 409306, H=250 mg BI 409306, M= 400 mg moxifloxacin, P=Placebo 1/Placebo 2.

Treatment:

Drug: Placebo matching to BI 409306

Drug: BI 409306

Drug: Moxifloxacin

P/H/L/M/P treatment sequence

Experimental group

Description:

In this randomized, placebo-controlled, 5-period crossover trial participants were randomized to one of 15 possible treatment sequences based on a balanced, Prescott triple Latin square design. Treatments administered were 50 mg BI 409306 administered orally as a single dose (1 film-coated tablet plus 4 film-coated placebo tablets), 250 mg BI 409306 administered orally as a single dose (5 film-coated tablets), 400 mg moxifloxacin administered orally as a single dose (1 film-coated tablet), Placebo 1 and Placebo 2 both administered orally as a single dose (5 film-coated tablets). In all treatment periods tablets were taken with 240 milliliter of water after an overnight fast of at least 10 hours on day 1 of the treatment period. The trial was double-blind for placebo and BI 409306, but open-label for moxifloxacin. A washout period of least 6 days was adhered to between drug administrations. L=50 mg BI 409306, H=250 mg BI 409306, M= 400 mg moxifloxacin, P=Placebo 1/Placebo 2.

Treatment:

Drug: Placebo matching to BI 409306

Drug: BI 409306

Drug: Moxifloxacin

P/H/L/P/M treatment sequence

Experimental group

Description:

In this randomized, placebo-controlled, 5-period crossover trial participants were randomized to one of 15 possible treatment sequences based on a balanced, Prescott triple Latin square design. Treatments administered were 50 mg BI 409306 administered orally as a single dose (1 film-coated tablet plus 4 film-coated placebo tablets), 250 mg BI 409306 administered orally as a single dose (5 film-coated tablets), 400 mg moxifloxacin administered orally as a single dose (1 film-coated tablet), Placebo 1 and Placebo 2 both administered orally as a single dose (5 film-coated tablets). In all treatment periods tablets were taken with 240 milliliter of water after an overnight fast of at least 10 hours on day 1 of the treatment period. The trial was double-blind for placebo and BI 409306, but open-label for moxifloxacin. A washout period of least 6 days was adhered to between drug administrations. L=50 mg BI 409306, H=250 mg BI 409306, M= 400 mg moxifloxacin, P=Placebo 1/Placebo 2.

Treatment:

Drug: Placebo matching to BI 409306

Drug: BI 409306

Drug: Moxifloxacin

P/L/M/P/H treatment sequence

Experimental group

Description:

In this randomized, placebo-controlled, 5-period crossover trial participants were randomized to one of 15 possible treatment sequences based on a balanced, Prescott triple Latin square design. Treatments administered were 50 mg BI 409306 administered orally as a single dose (1 film-coated tablet plus 4 film-coated placebo tablets), 250 mg BI 409306 administered orally as a single dose (5 film-coated tablets), 400 mg moxifloxacin administered orally as a single dose (1 film-coated tablet), Placebo 1 and Placebo 2 both administered orally as a single dose (5 film-coated tablets). In all treatment periods tablets were taken with 240 milliliter of water after an overnight fast of at least 10 hours on day 1 of the treatment period. The trial was double-blind for placebo and BI 409306, but open-label for moxifloxacin. A washout period of least 6 days was adhered to between drug administrations. L=50 mg BI 409306, H=250 mg BI 409306, M= 400 mg moxifloxacin, P=Placebo 1/Placebo 2.

Treatment:

Drug: Placebo matching to BI 409306

Drug: BI 409306

Drug: Moxifloxacin

P/M/P/L/H treatment sequence

Experimental group

Description:

In this randomized, placebo-controlled, 5-period crossover trial participants were randomized to one of 15 possible treatment sequences based on a balanced, Prescott triple Latin square design. Treatments administered were 50 mg BI 409306 administered orally as a single dose (1 film-coated tablet plus 4 film-coated placebo tablets), 250 mg BI 409306 administered orally as a single dose (5 film-coated tablets), 400 mg moxifloxacin administered orally as a single dose (1 film-coated tablet), Placebo 1 and Placebo 2 both administered orally as a single dose (5 film-coated tablets). In all treatment periods tablets were taken with 240 milliliter of water after an overnight fast of at least 10 hours on day 1 of the treatment period. The trial was double-blind for placebo and BI 409306, but open-label for moxifloxacin. A washout period of least 6 days was adhered to between drug administrations. L=50 mg BI 409306, H=250 mg BI 409306, M= 400 mg moxifloxacin, P=Placebo 1/Placebo 2.

Treatment:

Drug: Placebo matching to BI 409306

Drug: BI 409306

Drug: Moxifloxacin

P/P/L/H/M treatment sequence

Experimental group

Description:

In this randomized, placebo-controlled, 5-period crossover trial participants were randomized to one of 15 possible treatment sequences based on a balanced, Prescott triple Latin square design. Treatments administered were 50 mg BI 409306 administered orally as a single dose (1 film-coated tablet plus 4 film-coated placebo tablets), 250 mg BI 409306 administered orally as a single dose (5 film-coated tablets), 400 mg moxifloxacin administered orally as a single dose (1 film-coated tablet), Placebo 1 and Placebo 2 both administered orally as a single dose (5 film-coated tablets). In all treatment periods tablets were taken with 240 milliliter of water after an overnight fast of at least 10 hours on day 1 of the treatment period. The trial was double-blind for placebo and BI 409306, but open-label for moxifloxacin. A washout period of least 6 days was adhered to between drug administrations. L=50 mg BI 409306, H=250 mg BI 409306, M= 400 mg moxifloxacin, P=Placebo 1/Placebo 2.

Treatment:

Drug: Placebo matching to BI 409306

Drug: BI 409306

Drug: Moxifloxacin

P/P/M/L/H treatment sequence

Experimental group

Description:

In this randomized, placebo-controlled, 5-period crossover trial participants were randomized to one of 15 possible treatment sequences based on a balanced, Prescott triple Latin square design. Treatments administered were 50 mg BI 409306 administered orally as a single dose (1 film-coated tablet plus 4 film-coated placebo tablets), 250 mg BI 409306 administered orally as a single dose (5 film-coated tablets), 400 mg moxifloxacin administered orally as a single dose (1 film-coated tablet), Placebo 1 and Placebo 2 both administered orally as a single dose (5 film-coated tablets). In all treatment periods tablets were taken with 240 milliliter of water after an overnight fast of at least 10 hours on day 1 of the treatment period. The trial was double-blind for placebo and BI 409306, but open-label for moxifloxacin. A washout period of least 6 days was adhered to between drug administrations. L=50 mg BI 409306, H=250 mg BI 409306, M= 400 mg moxifloxacin, P=Placebo 1/Placebo 2.

Treatment:

Drug: Placebo matching to BI 409306

Drug: BI 409306

Drug: Moxifloxacin