Healthy
Conditions
Brief summary
To evaluate the photosensitivity potential of BI 730357
Interventions
Sponsors
Boehringer Ingelheim
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
* Healthy male and female subjects according to the assessment of the Investigator, based on a complete medical history, physical examination (including dermatological skin type assessment), vital signs (blood pressure, pulse rate), 12-lead ECG, and clinical laboratory tests * 18 to 55 years old * BMI 18 to 35 kg/m (incl.) * Fitzpatrick skin type I, II, or III: * I Always burns easily, never tans * II Always burns easily, tans minimally * III Burns moderately, tans gradually * No ultraviolet exposure of the test areas 4 weeks prior to baseline photo testing * Normal skin response during preliminary photo testing. * Signed and dated written informed consent in accordance with ICH-GCP and local legislation prior to admission to the trial. * Women of childbearing potential (WOCBP)1 must be ready and able to use highly effective methods of birth control per ICH M3 (R2) that result in a low failure rate of less than 1% per year when used consistently and correctly. A list of contraception methods meeting these criteria is provided in the patient information
Exclusion criteria
* Any finding in the medical examination (including blood pressure, pulse rate or ECG) deviating from normal and judged as clinically relevant by the Investigator. * Any laboratory value outside the reference range that the Investigator considers to be of clinical relevance. * Gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunological or hormonal disorders or any evidence of a concomitant disease judged as clinically relevant by the Investigator. * Major surgery (major according to the investigator's assessment) performed within 10 weeks prior to randomisation or planned within 2 months after screening. * Any documented active or suspected malignancy or history of malignancy within 5 years prior to screening, except appropriately treated basal cell carcinoma of the skin or in situ carcinoma of uterine cervix. * Active skin disorders on the back where photosensitivity testing will be performed. * Subjects who must or wish to continue the intake of restricted medications or any drug considered likely to interfere with the safe conduct of the trial. * Subjects not expected to comply with the protocol requirements or not expected to complete the trial as scheduled (e.g. chronic alcohol or drug abuse or any other condition that, in the investigator's opinion, makes the subject an unreliable trial participant). * Currently enrolled in another investigational device or drug trial, or less than 30 days (or 5 half-lives (whichever longer)) since ending another investigational drug trial. * Women who are pregnant, nursing, or who plan to become pregnant while in the trial. * History of relevant allergy or hypersensitivity (including allergy to the trial medication or its excipients). * History of hypersensitivity to ciprofloxacin, any member of the quinolone class of antibacterials. * History of hypersensitivity to sunlight or artificial source of intense light, especially UV light. * Chronic or acute infections which are of relevance in the opinion of the Investigator. * Positive result for HIV, HBV, and hepatitis C (Hep C) at screening. * History of TB or positive finding in IGRA. * Unwillingness/inability to refrain from intake of alcoholic beverages from 48 hours prior to the trial medication administration and until Day 7 post trial medication administration. * Positive drug screening. * Blood donation of more than 500 mL within 30 days prior to administration of trial medication or intended donation during the trial. * Intention to perform excessive physical activities within 4 days prior to administration of trial medication or contact sport during the entire trial and unwilling to avoid vigorous exercise for 7 days post dosing. * Inability to comply with dietary regimen of trial site. * Unwillingness to adhere to the rules of UV-light protection * Received a live vaccination within 12 weeks prior to randomisation (visit 2), or any plan to receive a live vaccination during the conduct of this trial. * Subjects with known prolongation of the QT interval, risk factors for QT prolongation or torsade de pointes.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Photosensitivity Index at 24 Hours Under Condition 1 (i.e., Under Full Range of UVB/UVA Exposure, Simulating Midday Summer Outdoor Sun Exposure) | At 24 hours after irradiation on Day 8 | Photosensitivity index (PI) under condition 1 (C1)(i.e., under full range solar UVB/UVA (290 to 400 nm, UBV content \ 10%), simulating midday summer outdoor sun exposure (assessed in μw/cm2)), was defined as ratio of the precise Minimum erythema dose (MED)baseline to MEDon-drug at each respective post irradiation time point (i.e. 24 hours)(i.e., MEDon-drug\[millijoules (mJ)\]/MEDbaseline\[mJ\]) and was hence unitless. MED was defined as lowest dose that produced uniform redness (C1) (assessed in mJ for UVB/UVA). Subjects were exposed to a series of 6 graded full range solar UVB/UVA exposures, each 25% greater than the previous dose. Light exposure occurred 2 hours (±10 minutes) after dose on Day 8 of either investigational product (IP) or placebo, and on-treatment photosensitivity assessments (determination of MEDon-drug + evaluation of erythema/local skin reactions) were performed at 24 hours after irradiation. |
| Photosensitivity Index at 24 Hours Under Condition 2 (i.e., Under UVA Exposure Only, Simulating Indoor Sun Exposure Behind Window Glass) | At 24 hours after irradiation on Day 8 | Photosensitivity index (PI) under condition 2 (C2)(i.e., UVA only (320 to 400 nm, UVB content \<0.03%), simulating indoor exposure behind window glass with a secondary assessment of erythema and local skin reactions at 25 Joules per centimetres-2 (J cm-2) (assessed in mw/cm2)), defined as ratio of the precise Minimum erythema dose (MED)baseline to MEDon-drug at each respective post irradiation time point (i.e. 24 hours)(i.e., MEDon-drug\[Joules (J)\]/MEDbaseline\[J\]) and hence unitless. MED was defined as lowest dose that produced uniform darkening (C2) (assessed in J for UVA). Subjects were exposed to series of 6 graded full range solar UVA exposures (C2), each 25% greater than the previous dose. Light exposure occurred 2 hours (±10 minutes) after dose on Day 8 of either investigational product (IP) or placebo, and on-treatment photosensitivity assessments (determination of MEDon-drug + evaluation of erythema/local skin reactions) were performed at 24 hours after irradiation. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Photosensitivity Index (PI) at 1 Hour Under Condition 1 (i.e., Under Full Range of UVB/UVA Exposure, Simulating Midday Summer Outdoor Sun Exposure) | At 1 hour after irradiation on Day 8 | Photosensitivity index (PI) under condition 1 (C1)(i.e., under full range solar UVB/UVA (290 to 400 nm, UBV content \ 10%), simulating midday summer outdoor sun exposure (assessed in μw/cm2)), was defined as ratio of the precise Minimum erythema dose (MED)baseline to MEDon-drug at each respective post irradiation time point (i.e. 1 hour)(i.e., MEDon-drug\[millijoules (mJ)\]/MEDbaseline\[mJ\]) and was hence unitless. MED was defined as lowest dose that produced uniform redness (C1) (assessed in mJ for UVB/UVA). Subjects were exposed to a series of 6 graded full range solar UVB/UVA exposures, each 25% greater than the previous dose. Light exposure occurred 2 hours (±10 minutes) after dose on Day 8 of either investigational product (IP) or placebo, and on-treatment photosensitivity assessments (determination of MEDon-drug + evaluation of erythema/local skin reactions) were performed at 1 hour after irradiation. |
| Photosensitivity Index (PI) at 1 Hour Under Condition 2 (i.e., Under UVA Exposure Only, Simulating Indoor Sun Exposure Behind Window Glass) | At 1 hour after irradiation on Day 8 | Photosensitivity index (PI) under condition 2 (C2)(i.e., UVA only (320 to 400 nm, UVB content \<0.03%), simulating indoor exposure behind window glass with a secondary assessment of erythema and local skin reactions at 25 Joules centimetres-2 (J cm-2) (assessed in mw/cm2)), defined as ratio of precise Minimum erythema dose (MED)baseline to MEDon-drug at each respective post irradiation time point (i.e. 1 hour)(i.e. MEDon-drug\[Joules (J)\]/MEDbaseline\[J\]) and was hence unitless. MED defined as lowest dose that produced uniform darkening (C2) (assessed in J for UVA). Subjects were exposed to series of 6 graded full range solar UVA only exposures (C2), each 25% greater than the previous dose. Light exposure occurred 2 hours (±10 minutes) after dose on Day 8 of either investigational product (IP) or placebo, and on-treatment photosensitivity assessments (determination of MEDon-drug + evaluation of erythema/local skin reactions) were performed at 1 hour after irradiation. |
| Minimum Erythema Dose (MED) Percent Change From Baseline at 10 Minutes Under Condition 1 (i.e., Under Full Range of UVB/UVA Exposure, Simulating Midday Summer Outdoor Sun Exposure) | At baseline (Day -2) and at 10 minutes after irradiation on Day 8 | The Minimum erythema dose (MED) percent change from baseline at 10 minutes was calculated as follows: % change = (\[MEDon-drug - MEDbaseline\]/ MEDbaseline) x 100. MED under condition 1 (C1)(i.e., under full range solar UVB/UVA (290 to 400 nm, UBV content \ 10%), simulating midday summer outdoor sun exposure (assessed in μw/cm2)), was defined as lowest dose that produced uniform redness (assessed in mJ for UVB/UVA). Subjects were exposed to a series of 6 graded full range solar UVB/UVA exposures, each 25% greater than the previous dose. Light exposure occurred 2 hours (±10 minutes) after dose on Day 8 of either investigational product (IP) or placebo, and on-treatment photosensitivity assessments (determination of MEDon-drug + evaluation of erythema/local skin reactions) were performed at 10 minutes after irradiation. |
| Minimum Erythema Dose (MED) Percent Change From Baseline at 10 Minutes Under Condition 2 (i.e., Under UVA Exposure Only, Simulating Indoor Sun Exposure Behind Window Glass) | At baseline (Day -2) and at 10 minutes after irradiation on Day 8 | The Minimum erythema dose (MED) percent change from baseline at 10 minutes was calculated as follows: % change = (\[MEDon-drug - MEDbaseline\]/ MEDbaseline) x 100. MED under condition 2 (C2)(i.e., UVA only (320 to 400 nm, UVB content \<0.03%), simulating indoor exposure behind window glass with a secondary assessment of erythema and local skin reactions at 25 Joules centimetres-2 (J cm-2) (assessed in mw/cm2)), was defined as lowest dose that produced uniform darkening (assessed in J for UVA). Subjects were exposed to a series of 6 graded full range solar UVA only exposures, each 25% greater than the previous dose. Light exposure occurred 2 hours (±10 minutes) after dose on Day 8 of either investigational product (IP) or placebo, and on-treatment photosensitivity assessments (determination of MEDon-drug + evaluation of erythema/local skin reactions) were performed at 10 minutes after irradiation. |
| Photosensitivity Index (PI) at 10 Minutes Under Condition 1 (i.e., Under Full Range of UVB/UVA Exposure, Simulating Midday Summer Outdoor Sun Exposure) | At 10 minutes after irradiation on Day 8 | Photosensitivity index (PI) under condition 1 (C1)(i.e., under full range solar UVB/UVA (290 to 400 nm, UBV content \ 10%), simulating midday summer outdoor sun exposure (assessed in μw/cm2)), was defined as ratio of the precise Minimum erythema dose (MED)baseline to MEDon-drug at each respective post irradiation time point (i.e. 10 minutes)(i.e., MEDon-drug\[millijoules (mJ)\]/MEDbaseline\[mJ\]) and was hence unitless. MED was defined as lowest dose that produced uniform redness (C1) (assessed in mJ for UVB/UVA). Subjects were exposed to a series of 6 graded full range solar UVB/UVA exposures, each 25% greater than the previous dose. Light exposure occurred 2 hours (±10 minutes) after dose on Day 8 of either investigational product (IP) or placebo, and on-treatment photosensitivity assessments (determination of MEDon-drug + evaluation of erythema/local skin reactions) were performed at 10 minutes after irradiation. |
| Minimum Erythema Dose (MED) Percent Change From Baseline at 1 Hour Under Condition 2 (i.e., Under UVA Exposure Only, Simulating Indoor Sun Exposure Behind Window Glass) | At baseline (Day -2) and at 1 hour after irradiation on Day 8 | The Minimum erythema dose (MED) percent change from baseline at 1 hour was calculated as follows: % change = (\[MEDon-drug - MEDbaseline\]/ MEDbaseline) x 100. MED under condition 2 (C2)(i.e., UVA only (320 to 400 nm, UVB content \<0.03%), simulating indoor exposure behind window glass with a secondary assessment of erythema and local skin reactions at 25 Joules centimetres-2 (J cm-2) (assessed in mw/cm2)), was defined as lowest dose that produced uniform darkening (assessed in J for UVA). Subjects were exposed to a series of 6 graded full range solar UVA only exposures, each 25% greater than the previous dose. Light exposure occurred 2 hours (±10 minutes) after dose on Day 8 of either investigational product (IP) or placebo, and on-treatment photosensitivity assessments (determination of MEDon-drug + evaluation of erythema/local skin reactions) were performed at 1 hour after irradiation. |
| Minimum Erythema Dose (MED) Percent Change From Baseline at 24 Hours Under Condition 1 (i.e., Under Full Range of UVB/UVA Exposure, Simulating Midday Summer Outdoor Sun Exposure) | At baseline (Day -2) and at 24 hours after irradiation on Day 8 | The Minimum erythema dose (MED) percent change from baseline at 24 hours was calculated as follows: % change = (\[MEDon-drug - MEDbaseline\]/ MEDbaseline) x 100. MED under condition 1 (C1)(i.e., under full range solar UVB/UVA (290 to 400 nm, UBV content \ 10%), simulating midday summer outdoor sun exposure (assessed in μw/cm2)), was defined as lowest dose that produced uniform redness (assessed in mJ for UVB/UVA). Subjects were exposed to a series of 6 graded full range solar UVB/UVA exposures, each 25% greater than the previous dose. Light exposure occurred 2 hours (±10 minutes) after dose on Day 8 of either investigational product (IP) or placebo, and on-treatment photosensitivity assessments (determination of MEDon-drug + evaluation of erythema/local skin reactions) were performed at 24 hours after irradiation. |
| Minimum Erythema Dose (MED) Percent Change From Baseline at 24 Hours Under Condition 2 (i.e., Under UVA Exposure Only, Simulating Indoor Sun Exposure Behind Window Glass) | At baseline and at 24 hours | The Minimum erythema dose (MED) percent change from baseline at 24 hours was calculated as follows: % change = (\[MEDon-drug - MEDbaseline\]/ MEDbaseline) x 100. MED under condition 2 (C2)(i.e., UVA only (320 to 400 nm, UVB content \<0.03%), simulating indoor exposure behind window glass with a secondary assessment of erythema and local skin reactions at 25 Joules centimetres-2 (J cm-2) (assessed in mw/cm2)), was defined as lowest dose that produced uniform darkening (assessed in J for UVA). Subjects were exposed to a series of 6 graded full range solar UVA only exposures, each 25% greater than the previous dose. Light exposure occurred 2 hours (±10 minutes) after dose on Day 8 of either investigational product (IP) or placebo, and on-treatment photosensitivity assessments (determination of MEDon-drug + evaluation of erythema/local skin reactions) were performed at 24 hours after irradiation. |
| Minimum Erythema Dose (MED) Percent Change From Baseline at 1 Hour Under Condition 1 (i.e., Under Full Range of UVB/UVA Exposure, Simulating Midday Summer Outdoor Sun Exposure) | At baseline (Day -2) and at 1 hour after irradiation on Day 8 | The Minimum erythema dose (MED) percent change from baseline at 1 hour was calculated as follows: % change = (\[MEDon-drug - MEDbaseline\]/ MEDbaseline) x 100. MED under condition 1 (C1)(i.e., under full range solar UVB/UVA (290 to 400 nm, UBV content \ 10%), simulating midday summer outdoor sun exposure (assessed in μw/cm2)), was defined as lowest dose that produced uniform redness (assessed in mJ for UVB/UVA). Subjects were exposed to a series of 6 graded full range solar UVB/UVA exposures, each 25% greater than the previous dose. Light exposure occurred 2 hours (±10 minutes) after dose on Day 8 of either investigational product (IP) or placebo, and on-treatment photosensitivity assessments (determination of MEDon-drug + evaluation of erythema/local skin reactions) were performed at 1 hour after irradiation. |
| Photosensitivity Index (PI) at 10 Minutes Under Condition 2 (i.e., Under UVA Exposure Only, Simulating Indoor Sun Exposure Behind Window Glass) | At 10 minutes after irradiation on Day 8 | Photosensitivity index (PI) under condition 2 (C2)(i.e., UVA only (320 to 400 nm, UVB content \<0.03%), simulating indoor exposure behind window glass with secondary assessment of erythema and local skin reactions at 25 Joules centimetres-2 (J cm-2) (assessed in mw/cm2)), was defined as ratio of precise Minimum erythema dose (MED)baseline to MEDon-drug at each respective post irradiation time point (i.e. 10 minutes)(i.e., MEDon-drug\[Joules (J)\]/MEDbaseline\[J\]) and was hence unitless. MED defined as lowest dose that produced uniform darkening (C2) (assessed in J for UVA). Subjects were exposed to series of 6 graded full range solar UVA exposures (C2), each 25% greater than the previous dose. Light exposure occurred 2 hours (±10 minutes) after dose on Day 8 of either investigational product (IP) or placebo, and on-treatment photosensitivity assessments (determination of MEDon-drug + evaluation of erythema/local skin reactions) were performed at 10 minutes after irradiation. |
Countries
United States
Participant flow
Recruitment details
This is a partially blind, randomized, parallel group, placebo, and active comparator controlled Phase I clinical trial in healthy male and female subjects to evaluate the photosensitivity potential of BI 730357 compared with placebo and active comparator, and to assess the relationship between the photosensitivity response and pharmacokinetics of BI 730357.
Pre-assignment details
All subjects were screened for eligibility to participants in the trial. Subjects attended specialist sites which would then ensure that they met all strictly implemented inclusion/exclusion criteria. Subjects were not to be assigned to treatment groups if any one of the specific entry criteria were violated.
Participants by arm
| Arm | Count |
|---|---|
| Placebo QD Subjects received orally, four Placebo film-coated tablets once per day (QD) over 8 days. Medication administration was to take place at the same time every day within a deviation of no more than ±15 minutes together with about 240 millilitres (mL) of water. | 9 |
| 400 mg QD BI 730357 Subjects received orally, four BI 730357 film-coated tablets of 100 miligrams (mg) each (400 mg in total) once per day (QD) over 8 days. Medication administration was to take place at the same time every day within a deviation of no more than ±15 minutes together with about 240 mL of water. | 27 |
| Placebo BID Subjects received orally, three Placebo film-coated tablets two times per day (BID) over 7 days with a single dose Placebo on Day 8. Medication administration was to take place at the same time every day within a deviation of no more than ±15 minutes together with about 240 mL of water. | 9 |
| 300 mg BID BI 730357 Subjects received orally, three BI 730357 film-coated tablets of 100 miligrams (mg) each, two times per day (BID) (2 x 300 mg = 600 mg daily dose in total) over 7 days with a single dose of 300 mg on Day 8. Medication administration was to take place at the same time every day within a deviation of no more than ±15 minutes together with about 240 mL of water. | 28 |
| 500 mg Ciprofloxacin (Active Comparator) Subjects received orally, one Ciprofloxacin film-coated tablet of 500 miligrams (mg) each, two times per days (BID) (2 x 500 mg = 1000 mg daily dose in total) over 5 days from day 3 with a single dose of 500 mg on Day 8. Medication administration was to take place at the same time every day within a deviation of no more than ±15 minutes together with about 240 mL of water. | 12 |
| Total | 85 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 | 1 | 2 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 0 | 1 | 1 | 0 |
Baseline characteristics
| Characteristic | Placebo QD | Total | 500 mg Ciprofloxacin (Active Comparator) | 300 mg BID BI 730357 | Placebo BID | 400 mg QD BI 730357 |
|---|---|---|---|---|---|---|
| Age, Continuous | 43.0 Years STANDARD_DEVIATION 12.06 | 39.4 Years STANDARD_DEVIATION 11.84 | 40.7 Years STANDARD_DEVIATION 12.58 | 39.7 Years STANDARD_DEVIATION 12.84 | 40.1 Years STANDARD_DEVIATION 8.84 | 37.0 Years STANDARD_DEVIATION 11.62 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 4 Participants | 41 Participants | 5 Participants | 12 Participants | 6 Participants | 14 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 5 Participants | 44 Participants | 7 Participants | 16 Participants | 3 Participants | 13 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Minimum Erythema Dose (MED) at baseline under condition 1 | 30.60 millijoules/squarecentimeter STANDARD_DEVIATION 6.328 | 32.89 millijoules/squarecentimeter STANDARD_DEVIATION 11.34 | 30.78 millijoules/squarecentimeter STANDARD_DEVIATION 12.28 | 30.82 millijoules/squarecentimeter STANDARD_DEVIATION 12.163 | 36.84 millijoules/squarecentimeter STANDARD_DEVIATION 7.91 | 35.41 millijoules/squarecentimeter STANDARD_DEVIATION 11.892 |
| Minimum Erythema Dose (MED) at baseline under condition 2 | 21.60 Joules/squarecentimeter STANDARD_DEVIATION 4.04 | 22.67 Joules/squarecentimeter STANDARD_DEVIATION 4.25 | 22.58 Joules/squarecentimeter STANDARD_DEVIATION 4.64 | 20.83 Joules/squarecentimeter STANDARD_DEVIATION 5.29 | 25.10 Joules/squarecentimeter STANDARD_DEVIATION 0 | 24.09 Joules/squarecentimeter STANDARD_DEVIATION 2.76 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 2 Participants | 0 Participants | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 2 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) White | 9 Participants | 80 Participants | 12 Participants | 26 Participants | 7 Participants | 26 Participants |
| Sex: Female, Male Female | 4 Participants | 43 Participants | 3 Participants | 18 Participants | 6 Participants | 12 Participants |
| Sex: Female, Male Male | 5 Participants | 42 Participants | 9 Participants | 10 Participants | 3 Participants | 15 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 18 | 0 / 27 | 0 / 28 | 0 / 12 |
| other Total, other adverse events | 7 / 18 | 9 / 27 | 11 / 28 | 4 / 12 |
| serious Total, serious adverse events | 0 / 18 | 0 / 27 | 0 / 28 | 0 / 12 |
Outcome results
Primary
Photosensitivity Index at 24 Hours Under Condition 1 (i.e., Under Full Range of UVB/UVA Exposure, Simulating Midday Summer Outdoor Sun Exposure)
Photosensitivity index (PI) under condition 1 (C1)(i.e., under full range solar UVB/UVA (290 to 400 nm, UBV content \ 10%), simulating midday summer outdoor sun exposure (assessed in μw/cm2)), was defined as ratio of the precise Minimum erythema dose (MED)baseline to MEDon-drug at each respective post irradiation time point (i.e. 24 hours)(i.e., MEDon-drug\[millijoules (mJ)\]/MEDbaseline\[mJ\]) and was hence unitless. MED was defined as lowest dose that produced uniform redness (C1) (assessed in mJ for UVB/UVA). Subjects were exposed to a series of 6 graded full range solar UVB/UVA exposures, each 25% greater than the previous dose. Light exposure occurred 2 hours (±10 minutes) after dose on Day 8 of either investigational product (IP) or placebo, and on-treatment photosensitivity assessments (determination of MEDon-drug + evaluation of erythema/local skin reactions) were performed at 24 hours after irradiation.
Time frame: At 24 hours after irradiation on Day 8
Population: Full Analysis Set (FAS): This set included all subjects in the treated set (TS) who provided at least 1 photosensitivity endpoint that was defined as primary or secondary and was not excluded due to a protocol deviation relevant to the evaluation of photosensitivity.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo QD | Photosensitivity Index at 24 Hours Under Condition 1 (i.e., Under Full Range of UVB/UVA Exposure, Simulating Midday Summer Outdoor Sun Exposure) | 0.93 Unitless |
| 400 mg QD BI 730357 | Photosensitivity Index at 24 Hours Under Condition 1 (i.e., Under Full Range of UVB/UVA Exposure, Simulating Midday Summer Outdoor Sun Exposure) | 1.01 Unitless |
| Placebo BID | Photosensitivity Index at 24 Hours Under Condition 1 (i.e., Under Full Range of UVB/UVA Exposure, Simulating Midday Summer Outdoor Sun Exposure) | 1.00 Unitless |
| 300 mg BID BI 730357 | Photosensitivity Index at 24 Hours Under Condition 1 (i.e., Under Full Range of UVB/UVA Exposure, Simulating Midday Summer Outdoor Sun Exposure) | 1.04 Unitless |
| 500 mg Ciprofloxacin (Active Comparator) | Photosensitivity Index at 24 Hours Under Condition 1 (i.e., Under Full Range of UVB/UVA Exposure, Simulating Midday Summer Outdoor Sun Exposure) | 1.08 Unitless |
Comparison: Mixed model for repeated measures (MMRM) with unstructured (UN) covariance matrix on photosensitivity index (PI) values90% CI: [-0.03, 0.2]Linear mixed model
Comparison: Mixed model for repeated measures (MMRM) with unstructured (UN) covariance matrix on photosensitivity index (PI) values90% CI: [-0.07, 0.16]Linear mixed model
p-value: 0.57290% CI: [-0.14, 0.08]Linear mixed model
p-value: 0.31590% CI: [-0.07, 0.23]Linear mixed model
p-value: 0.28690% CI: [-0.18, 0.05]Linear mixed model
p-value: 0.05790% CI: [0, 0.31]Linear mixed model
Primary
Photosensitivity Index at 24 Hours Under Condition 2 (i.e., Under UVA Exposure Only, Simulating Indoor Sun Exposure Behind Window Glass)
Photosensitivity index (PI) under condition 2 (C2)(i.e., UVA only (320 to 400 nm, UVB content \<0.03%), simulating indoor exposure behind window glass with a secondary assessment of erythema and local skin reactions at 25 Joules per centimetres-2 (J cm-2) (assessed in mw/cm2)), defined as ratio of the precise Minimum erythema dose (MED)baseline to MEDon-drug at each respective post irradiation time point (i.e. 24 hours)(i.e., MEDon-drug\[Joules (J)\]/MEDbaseline\[J\]) and hence unitless. MED was defined as lowest dose that produced uniform darkening (C2) (assessed in J for UVA). Subjects were exposed to series of 6 graded full range solar UVA exposures (C2), each 25% greater than the previous dose. Light exposure occurred 2 hours (±10 minutes) after dose on Day 8 of either investigational product (IP) or placebo, and on-treatment photosensitivity assessments (determination of MEDon-drug + evaluation of erythema/local skin reactions) were performed at 24 hours after irradiation.
Time frame: At 24 hours after irradiation on Day 8
Population: Full Analysis Set (FAS): This set included all subjects in the treated set (TS) who provided at least 1 photosensitivity endpoint that was defined as primary or secondary and was not excluded due to a protocol deviation relevant to the evaluation of photosensitivity.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo QD | Photosensitivity Index at 24 Hours Under Condition 2 (i.e., Under UVA Exposure Only, Simulating Indoor Sun Exposure Behind Window Glass) | 0.94 Unitless |
| 400 mg QD BI 730357 | Photosensitivity Index at 24 Hours Under Condition 2 (i.e., Under UVA Exposure Only, Simulating Indoor Sun Exposure Behind Window Glass) | 1.17 Unitless |
| Placebo BID | Photosensitivity Index at 24 Hours Under Condition 2 (i.e., Under UVA Exposure Only, Simulating Indoor Sun Exposure Behind Window Glass) | 1.00 Unitless |
| 300 mg BID BI 730357 | Photosensitivity Index at 24 Hours Under Condition 2 (i.e., Under UVA Exposure Only, Simulating Indoor Sun Exposure Behind Window Glass) | 1.01 Unitless |
| 500 mg Ciprofloxacin (Active Comparator) | Photosensitivity Index at 24 Hours Under Condition 2 (i.e., Under UVA Exposure Only, Simulating Indoor Sun Exposure Behind Window Glass) | 1.52 Unitless |
Comparison: Mixed model for repeated measures (MMRM) with unstructured (UN) covariance matrix on photosensitivity index (PI) values90% CI: [-0.02, 0.49]Linear mixed model
Comparison: Mixed model for repeated measures (MMRM) with unstructured (UN) covariance matrix on photosensitivity index (PI) values90% CI: [-0.2, 0.22]Linear mixed model
p-value: <0.00190% CI: [-0.72, -0.31]Linear mixed model
p-value: <0.00190% CI: [0.24, 0.8]Linear mixed model
p-value: 0.0190% CI: [-0.62, -0.09]Linear mixed model
p-value: 0.00190% CI: [0.24, 0.93]Linear mixed model
Secondary
Minimum Erythema Dose (MED) Percent Change From Baseline at 10 Minutes Under Condition 1 (i.e., Under Full Range of UVB/UVA Exposure, Simulating Midday Summer Outdoor Sun Exposure)
The Minimum erythema dose (MED) percent change from baseline at 10 minutes was calculated as follows: % change = (\[MEDon-drug - MEDbaseline\]/ MEDbaseline) x 100. MED under condition 1 (C1)(i.e., under full range solar UVB/UVA (290 to 400 nm, UBV content \ 10%), simulating midday summer outdoor sun exposure (assessed in μw/cm2)), was defined as lowest dose that produced uniform redness (assessed in mJ for UVB/UVA). Subjects were exposed to a series of 6 graded full range solar UVB/UVA exposures, each 25% greater than the previous dose. Light exposure occurred 2 hours (±10 minutes) after dose on Day 8 of either investigational product (IP) or placebo, and on-treatment photosensitivity assessments (determination of MEDon-drug + evaluation of erythema/local skin reactions) were performed at 10 minutes after irradiation.
Time frame: At baseline (Day -2) and at 10 minutes after irradiation on Day 8
Population: Full Analysis Set (FAS): This set included all subjects in the treated set (TS) who provided at least 1 photosensitivity endpoint that was defined as primary or secondary and was not excluded due to a protocol deviation relevant to the evaluation of photosensitivity.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo QD | Minimum Erythema Dose (MED) Percent Change From Baseline at 10 Minutes Under Condition 1 (i.e., Under Full Range of UVB/UVA Exposure, Simulating Midday Summer Outdoor Sun Exposure) | 3.12 Percent change |
| 400 mg QD BI 730357 | Minimum Erythema Dose (MED) Percent Change From Baseline at 10 Minutes Under Condition 1 (i.e., Under Full Range of UVB/UVA Exposure, Simulating Midday Summer Outdoor Sun Exposure) | 1.68 Percent change |
| Placebo BID | Minimum Erythema Dose (MED) Percent Change From Baseline at 10 Minutes Under Condition 1 (i.e., Under Full Range of UVB/UVA Exposure, Simulating Midday Summer Outdoor Sun Exposure) | 0.00 Percent change |
| 300 mg BID BI 730357 | Minimum Erythema Dose (MED) Percent Change From Baseline at 10 Minutes Under Condition 1 (i.e., Under Full Range of UVB/UVA Exposure, Simulating Midday Summer Outdoor Sun Exposure) | -1.96 Percent change |
| 500 mg Ciprofloxacin (Active Comparator) | Minimum Erythema Dose (MED) Percent Change From Baseline at 10 Minutes Under Condition 1 (i.e., Under Full Range of UVB/UVA Exposure, Simulating Midday Summer Outdoor Sun Exposure) | 0.00 Percent change |
p-value: 0.69290% CI: [-11.92, 7.99]Linear mixed model
p-value: 0.6390% CI: [-10.14, 6.21]Linear mixed model
p-value: 190% CI: [-11.07, 11.07]Linear mixed model
p-value: 0.75190% CI: [-10.55, 7.66]Linear mixed model
p-value: 0.66990% CI: [-6.17, 9.52]Linear mixed model
p-value: 0.54690% CI: [-13.44, 7.21]Linear mixed model
Secondary
Minimum Erythema Dose (MED) Percent Change From Baseline at 10 Minutes Under Condition 2 (i.e., Under UVA Exposure Only, Simulating Indoor Sun Exposure Behind Window Glass)
The Minimum erythema dose (MED) percent change from baseline at 10 minutes was calculated as follows: % change = (\[MEDon-drug - MEDbaseline\]/ MEDbaseline) x 100. MED under condition 2 (C2)(i.e., UVA only (320 to 400 nm, UVB content \<0.03%), simulating indoor exposure behind window glass with a secondary assessment of erythema and local skin reactions at 25 Joules centimetres-2 (J cm-2) (assessed in mw/cm2)), was defined as lowest dose that produced uniform darkening (assessed in J for UVA). Subjects were exposed to a series of 6 graded full range solar UVA only exposures, each 25% greater than the previous dose. Light exposure occurred 2 hours (±10 minutes) after dose on Day 8 of either investigational product (IP) or placebo, and on-treatment photosensitivity assessments (determination of MEDon-drug + evaluation of erythema/local skin reactions) were performed at 10 minutes after irradiation.
Time frame: At baseline (Day -2) and at 10 minutes after irradiation on Day 8
Population: Full Analysis Set (FAS): This set included all subjects in the treated set (TS) who provided at least 1 photosensitivity endpoint that was defined as primary or secondary and was not excluded due to a protocol deviation relevant to the evaluation of photosensitivity.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo QD | Minimum Erythema Dose (MED) Percent Change From Baseline at 10 Minutes Under Condition 2 (i.e., Under UVA Exposure Only, Simulating Indoor Sun Exposure Behind Window Glass) | 7.19 Percent change |
| 400 mg QD BI 730357 | Minimum Erythema Dose (MED) Percent Change From Baseline at 10 Minutes Under Condition 2 (i.e., Under UVA Exposure Only, Simulating Indoor Sun Exposure Behind Window Glass) | -1.02 Percent change |
| Placebo BID | Minimum Erythema Dose (MED) Percent Change From Baseline at 10 Minutes Under Condition 2 (i.e., Under UVA Exposure Only, Simulating Indoor Sun Exposure Behind Window Glass) | 0.00 Percent change |
| 300 mg BID BI 730357 | Minimum Erythema Dose (MED) Percent Change From Baseline at 10 Minutes Under Condition 2 (i.e., Under UVA Exposure Only, Simulating Indoor Sun Exposure Behind Window Glass) | -12.45 Percent change |
| 500 mg Ciprofloxacin (Active Comparator) | Minimum Erythema Dose (MED) Percent Change From Baseline at 10 Minutes Under Condition 2 (i.e., Under UVA Exposure Only, Simulating Indoor Sun Exposure Behind Window Glass) | 3.69 Percent change |
p-value: 0.28190% CI: [-35.44, 10.54]Linear mixed model
p-value: 0.09290% CI: [-35.02, 2.74]Linear mixed model
p-value: 0.77290% CI: [-21.88, 29.27]Linear mixed model
p-value: 0.53990% CI: [-34.93, 18.5]Linear mixed model
p-value: 0.68290% CI: [-27.74, 18.31]Linear mixed model
p-value: 0.81790% CI: [-33.79, 26.79]Linear mixed model
Secondary
Minimum Erythema Dose (MED) Percent Change From Baseline at 1 Hour Under Condition 1 (i.e., Under Full Range of UVB/UVA Exposure, Simulating Midday Summer Outdoor Sun Exposure)
The Minimum erythema dose (MED) percent change from baseline at 1 hour was calculated as follows: % change = (\[MEDon-drug - MEDbaseline\]/ MEDbaseline) x 100. MED under condition 1 (C1)(i.e., under full range solar UVB/UVA (290 to 400 nm, UBV content \ 10%), simulating midday summer outdoor sun exposure (assessed in μw/cm2)), was defined as lowest dose that produced uniform redness (assessed in mJ for UVB/UVA). Subjects were exposed to a series of 6 graded full range solar UVB/UVA exposures, each 25% greater than the previous dose. Light exposure occurred 2 hours (±10 minutes) after dose on Day 8 of either investigational product (IP) or placebo, and on-treatment photosensitivity assessments (determination of MEDon-drug + evaluation of erythema/local skin reactions) were performed at 1 hour after irradiation.
Time frame: At baseline (Day -2) and at 1 hour after irradiation on Day 8
Population: Full Analysis Set (FAS): This set included all subjects in the treated set (TS) who provided at least 1 photosensitivity endpoint that was defined as primary or secondary and was not excluded due to a protocol deviation relevant to the evaluation of photosensitivity.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo QD | Minimum Erythema Dose (MED) Percent Change From Baseline at 1 Hour Under Condition 1 (i.e., Under Full Range of UVB/UVA Exposure, Simulating Midday Summer Outdoor Sun Exposure) | -4.50 Percent change |
| 400 mg QD BI 730357 | Minimum Erythema Dose (MED) Percent Change From Baseline at 1 Hour Under Condition 1 (i.e., Under Full Range of UVB/UVA Exposure, Simulating Midday Summer Outdoor Sun Exposure) | 2.29 Percent change |
| Placebo BID | Minimum Erythema Dose (MED) Percent Change From Baseline at 1 Hour Under Condition 1 (i.e., Under Full Range of UVB/UVA Exposure, Simulating Midday Summer Outdoor Sun Exposure) | -2.85 Percent change |
| 300 mg BID BI 730357 | Minimum Erythema Dose (MED) Percent Change From Baseline at 1 Hour Under Condition 1 (i.e., Under Full Range of UVB/UVA Exposure, Simulating Midday Summer Outdoor Sun Exposure) | -3.59 Percent change |
| 500 mg Ciprofloxacin (Active Comparator) | Minimum Erythema Dose (MED) Percent Change From Baseline at 1 Hour Under Condition 1 (i.e., Under Full Range of UVB/UVA Exposure, Simulating Midday Summer Outdoor Sun Exposure) | 0.00 Percent change |
p-value: 0.89190% CI: [-11.49, 10.02]Linear mixed model
p-value: 0.41790% CI: [-12.42, 5.25]Linear mixed model
p-value: 0.63390% CI: [-9.11, 14.82]Linear mixed model
p-value: 0.12990% CI: [-2.05, 15.62]Linear mixed model
p-value: 0.54890% CI: [-5.33, 9.9]Linear mixed model
p-value: 0.3790% CI: [-5.51, 14.52]Linear mixed model
Secondary
Minimum Erythema Dose (MED) Percent Change From Baseline at 1 Hour Under Condition 2 (i.e., Under UVA Exposure Only, Simulating Indoor Sun Exposure Behind Window Glass)
The Minimum erythema dose (MED) percent change from baseline at 1 hour was calculated as follows: % change = (\[MEDon-drug - MEDbaseline\]/ MEDbaseline) x 100. MED under condition 2 (C2)(i.e., UVA only (320 to 400 nm, UVB content \<0.03%), simulating indoor exposure behind window glass with a secondary assessment of erythema and local skin reactions at 25 Joules centimetres-2 (J cm-2) (assessed in mw/cm2)), was defined as lowest dose that produced uniform darkening (assessed in J for UVA). Subjects were exposed to a series of 6 graded full range solar UVA only exposures, each 25% greater than the previous dose. Light exposure occurred 2 hours (±10 minutes) after dose on Day 8 of either investigational product (IP) or placebo, and on-treatment photosensitivity assessments (determination of MEDon-drug + evaluation of erythema/local skin reactions) were performed at 1 hour after irradiation.
Time frame: At baseline (Day -2) and at 1 hour after irradiation on Day 8
Population: Full Analysis Set (FAS): This set included all subjects in the treated set (TS) who provided at least 1 photosensitivity endpoint that was defined as primary or secondary and was not excluded due to a protocol deviation relevant to the evaluation of photosensitivity.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo QD | Minimum Erythema Dose (MED) Percent Change From Baseline at 1 Hour Under Condition 2 (i.e., Under UVA Exposure Only, Simulating Indoor Sun Exposure Behind Window Glass) | 13.82 Percent change |
| 400 mg QD BI 730357 | Minimum Erythema Dose (MED) Percent Change From Baseline at 1 Hour Under Condition 2 (i.e., Under UVA Exposure Only, Simulating Indoor Sun Exposure Behind Window Glass) | -12.82 Percent change |
| Placebo BID | Minimum Erythema Dose (MED) Percent Change From Baseline at 1 Hour Under Condition 2 (i.e., Under UVA Exposure Only, Simulating Indoor Sun Exposure Behind Window Glass) | 0.00 Percent change |
| 300 mg BID BI 730357 | Minimum Erythema Dose (MED) Percent Change From Baseline at 1 Hour Under Condition 2 (i.e., Under UVA Exposure Only, Simulating Indoor Sun Exposure Behind Window Glass) | -9.30 Percent change |
| 500 mg Ciprofloxacin (Active Comparator) | Minimum Erythema Dose (MED) Percent Change From Baseline at 1 Hour Under Condition 2 (i.e., Under UVA Exposure Only, Simulating Indoor Sun Exposure Behind Window Glass) | 2.19 Percent change |
p-value: 0.37590% CI: [-30.26, 11.66]Linear mixed model
p-value: 0.18590% CI: [-28.7, 5.73]Linear mixed model
p-value: 0.85190% CI: [-21.12, 25.5]Linear mixed model
p-value: 0.00790% CI: [-45.59, -7.69]Linear mixed model
p-value: 0.07190% CI: [-31.34, 1.33]Linear mixed model
p-value: 0.28190% CI: [-33.13, 9.86]Linear mixed model
Secondary
Minimum Erythema Dose (MED) Percent Change From Baseline at 24 Hours Under Condition 1 (i.e., Under Full Range of UVB/UVA Exposure, Simulating Midday Summer Outdoor Sun Exposure)
The Minimum erythema dose (MED) percent change from baseline at 24 hours was calculated as follows: % change = (\[MEDon-drug - MEDbaseline\]/ MEDbaseline) x 100. MED under condition 1 (C1)(i.e., under full range solar UVB/UVA (290 to 400 nm, UBV content \ 10%), simulating midday summer outdoor sun exposure (assessed in μw/cm2)), was defined as lowest dose that produced uniform redness (assessed in mJ for UVB/UVA). Subjects were exposed to a series of 6 graded full range solar UVB/UVA exposures, each 25% greater than the previous dose. Light exposure occurred 2 hours (±10 minutes) after dose on Day 8 of either investigational product (IP) or placebo, and on-treatment photosensitivity assessments (determination of MEDon-drug + evaluation of erythema/local skin reactions) were performed at 24 hours after irradiation.
Time frame: At baseline (Day -2) and at 24 hours after irradiation on Day 8
Population: Full Analysis Set (FAS): This set included all subjects in the treated set (TS) who provided at least 1 photosensitivity endpoint that was defined as primary or secondary and was not excluded due to a protocol deviation relevant to the evaluation of photosensitivity.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo QD | Minimum Erythema Dose (MED) Percent Change From Baseline at 24 Hours Under Condition 1 (i.e., Under Full Range of UVB/UVA Exposure, Simulating Midday Summer Outdoor Sun Exposure) | 9.35 Percent change |
| 400 mg QD BI 730357 | Minimum Erythema Dose (MED) Percent Change From Baseline at 24 Hours Under Condition 1 (i.e., Under Full Range of UVB/UVA Exposure, Simulating Midday Summer Outdoor Sun Exposure) | 1.35 Percent change |
| Placebo BID | Minimum Erythema Dose (MED) Percent Change From Baseline at 24 Hours Under Condition 1 (i.e., Under Full Range of UVB/UVA Exposure, Simulating Midday Summer Outdoor Sun Exposure) | 0.00 Percent change |
| 300 mg BID BI 730357 | Minimum Erythema Dose (MED) Percent Change From Baseline at 24 Hours Under Condition 1 (i.e., Under Full Range of UVB/UVA Exposure, Simulating Midday Summer Outdoor Sun Exposure) | -2.84 Percent change |
| 500 mg Ciprofloxacin (Active Comparator) | Minimum Erythema Dose (MED) Percent Change From Baseline at 24 Hours Under Condition 1 (i.e., Under Full Range of UVB/UVA Exposure, Simulating Midday Summer Outdoor Sun Exposure) | -3.83 Percent change |
p-value: 0.59990% CI: [-13.69, 8]Linear mixed model
p-value: 0.82490% CI: [-7.92, 9.9]Linear mixed model
p-value: 0.52590% CI: [-15.9, 8.23]Linear mixed model
p-value: 0.2590% CI: [-21.84, 5.84]Linear mixed model
p-value: 0.38690% CI: [-6.74, 17.12]Linear mixed model
p-value: 0.09790% CI: [-28.88, 2.51]Linear mixed model
Secondary
Minimum Erythema Dose (MED) Percent Change From Baseline at 24 Hours Under Condition 2 (i.e., Under UVA Exposure Only, Simulating Indoor Sun Exposure Behind Window Glass)
The Minimum erythema dose (MED) percent change from baseline at 24 hours was calculated as follows: % change = (\[MEDon-drug - MEDbaseline\]/ MEDbaseline) x 100. MED under condition 2 (C2)(i.e., UVA only (320 to 400 nm, UVB content \<0.03%), simulating indoor exposure behind window glass with a secondary assessment of erythema and local skin reactions at 25 Joules centimetres-2 (J cm-2) (assessed in mw/cm2)), was defined as lowest dose that produced uniform darkening (assessed in J for UVA). Subjects were exposed to a series of 6 graded full range solar UVA only exposures, each 25% greater than the previous dose. Light exposure occurred 2 hours (±10 minutes) after dose on Day 8 of either investigational product (IP) or placebo, and on-treatment photosensitivity assessments (determination of MEDon-drug + evaluation of erythema/local skin reactions) were performed at 24 hours after irradiation.
Time frame: At baseline and at 24 hours
Population: Full Analysis Set (FAS): This set included all subjects in the treated set (TS) who provided at least 1 photosensitivity endpoint that was defined as primary or secondary and was not excluded due to a protocol deviation relevant to the evaluation of photosensitivity.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo QD | Minimum Erythema Dose (MED) Percent Change From Baseline at 24 Hours Under Condition 2 (i.e., Under UVA Exposure Only, Simulating Indoor Sun Exposure Behind Window Glass) | 10.71 Percent change |
| 400 mg QD BI 730357 | Minimum Erythema Dose (MED) Percent Change From Baseline at 24 Hours Under Condition 2 (i.e., Under UVA Exposure Only, Simulating Indoor Sun Exposure Behind Window Glass) | -9.41 Percent change |
| Placebo BID | Minimum Erythema Dose (MED) Percent Change From Baseline at 24 Hours Under Condition 2 (i.e., Under UVA Exposure Only, Simulating Indoor Sun Exposure Behind Window Glass) | 0.00 Percent change |
| 300 mg BID BI 730357 | Minimum Erythema Dose (MED) Percent Change From Baseline at 24 Hours Under Condition 2 (i.e., Under UVA Exposure Only, Simulating Indoor Sun Exposure Behind Window Glass) | 0.99 Percent change |
| 500 mg Ciprofloxacin (Active Comparator) | Minimum Erythema Dose (MED) Percent Change From Baseline at 24 Hours Under Condition 2 (i.e., Under UVA Exposure Only, Simulating Indoor Sun Exposure Behind Window Glass) | -27.91 Percent change |
p-value: 0.88590% CI: [-12.83, 14.81]Linear mixed model
p-value: <0.00190% CI: [17.55, 40.25]Linear mixed model
p-value: <0.00190% CI: [-43.28, -12.54]Linear mixed model
p-value: 0.01690% CI: [-36.33, -3.92]Linear mixed model
p-value: 0.01190% CI: [4.53, 32.46]Linear mixed model
p-value: <0.00190% CI: [-57, -20.25]Linear mixed model
Secondary
Photosensitivity Index (PI) at 10 Minutes Under Condition 1 (i.e., Under Full Range of UVB/UVA Exposure, Simulating Midday Summer Outdoor Sun Exposure)
Photosensitivity index (PI) under condition 1 (C1)(i.e., under full range solar UVB/UVA (290 to 400 nm, UBV content \ 10%), simulating midday summer outdoor sun exposure (assessed in μw/cm2)), was defined as ratio of the precise Minimum erythema dose (MED)baseline to MEDon-drug at each respective post irradiation time point (i.e. 10 minutes)(i.e., MEDon-drug\[millijoules (mJ)\]/MEDbaseline\[mJ\]) and was hence unitless. MED was defined as lowest dose that produced uniform redness (C1) (assessed in mJ for UVB/UVA). Subjects were exposed to a series of 6 graded full range solar UVB/UVA exposures, each 25% greater than the previous dose. Light exposure occurred 2 hours (±10 minutes) after dose on Day 8 of either investigational product (IP) or placebo, and on-treatment photosensitivity assessments (determination of MEDon-drug + evaluation of erythema/local skin reactions) were performed at 10 minutes after irradiation.
Time frame: At 10 minutes after irradiation on Day 8
Population: Full Analysis Set (FAS): This set included all subjects in the treated set (TS) who provided at least 1 photosensitivity endpoint that was defined as primary or secondary and was not excluded due to a protocol deviation relevant to the evaluation of photosensitivity.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo QD | Photosensitivity Index (PI) at 10 Minutes Under Condition 1 (i.e., Under Full Range of UVB/UVA Exposure, Simulating Midday Summer Outdoor Sun Exposure) | 0.98 Unitless |
| 400 mg QD BI 730357 | Photosensitivity Index (PI) at 10 Minutes Under Condition 1 (i.e., Under Full Range of UVB/UVA Exposure, Simulating Midday Summer Outdoor Sun Exposure) | 1.00 Unitless |
| Placebo BID | Photosensitivity Index (PI) at 10 Minutes Under Condition 1 (i.e., Under Full Range of UVB/UVA Exposure, Simulating Midday Summer Outdoor Sun Exposure) | 1.00 Unitless |
| 300 mg BID BI 730357 | Photosensitivity Index (PI) at 10 Minutes Under Condition 1 (i.e., Under Full Range of UVB/UVA Exposure, Simulating Midday Summer Outdoor Sun Exposure) | 1.06 Unitless |
| 500 mg Ciprofloxacin (Active Comparator) | Photosensitivity Index (PI) at 10 Minutes Under Condition 1 (i.e., Under Full Range of UVB/UVA Exposure, Simulating Midday Summer Outdoor Sun Exposure) | 1.00 Unitless |
Comparison: Mixed model for repeated measures (MMRM) with unstructured (UN) covariance matrix on photosensitivity index (PI) values90% CI: [-0.05, 0.1]Linear mixed model
p-value: 0.99890% CI: [-0.08, 0.08]Linear mixed model
p-value: 0.61890% CI: [-0.08, 0.13]Linear mixed model
Comparison: Mixed model for repeated measures (MMRM) with unstructured (UN) covariance matrix on photosensitivity index (PI) values90% CI: [-0.1, 0.23]Linear mixed model
p-value: 0.45190% CI: [-0.1, 0.23]Linear mixed model
p-value: 190% CI: [-0.22, 0.22]Linear mixed model
Secondary
Photosensitivity Index (PI) at 10 Minutes Under Condition 2 (i.e., Under UVA Exposure Only, Simulating Indoor Sun Exposure Behind Window Glass)
Photosensitivity index (PI) under condition 2 (C2)(i.e., UVA only (320 to 400 nm, UVB content \<0.03%), simulating indoor exposure behind window glass with secondary assessment of erythema and local skin reactions at 25 Joules centimetres-2 (J cm-2) (assessed in mw/cm2)), was defined as ratio of precise Minimum erythema dose (MED)baseline to MEDon-drug at each respective post irradiation time point (i.e. 10 minutes)(i.e., MEDon-drug\[Joules (J)\]/MEDbaseline\[J\]) and was hence unitless. MED defined as lowest dose that produced uniform darkening (C2) (assessed in J for UVA). Subjects were exposed to series of 6 graded full range solar UVA exposures (C2), each 25% greater than the previous dose. Light exposure occurred 2 hours (±10 minutes) after dose on Day 8 of either investigational product (IP) or placebo, and on-treatment photosensitivity assessments (determination of MEDon-drug + evaluation of erythema/local skin reactions) were performed at 10 minutes after irradiation.
Time frame: At 10 minutes after irradiation on Day 8
Population: Full Analysis Set (FAS): This set included all subjects in the treated set (TS) who provided at least 1 photosensitivity endpoint that was defined as primary or secondary and was not excluded due to a protocol deviation relevant to the evaluation of photosensitivity.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo QD | Photosensitivity Index (PI) at 10 Minutes Under Condition 2 (i.e., Under UVA Exposure Only, Simulating Indoor Sun Exposure Behind Window Glass) | 1.02 Unitless |
| 400 mg QD BI 730357 | Photosensitivity Index (PI) at 10 Minutes Under Condition 2 (i.e., Under UVA Exposure Only, Simulating Indoor Sun Exposure Behind Window Glass) | 1.13 Unitless |
| Placebo BID | Photosensitivity Index (PI) at 10 Minutes Under Condition 2 (i.e., Under UVA Exposure Only, Simulating Indoor Sun Exposure Behind Window Glass) | 1.00 Unitless |
| 300 mg BID BI 730357 | Photosensitivity Index (PI) at 10 Minutes Under Condition 2 (i.e., Under UVA Exposure Only, Simulating Indoor Sun Exposure Behind Window Glass) | 1.29 Unitless |
| 500 mg Ciprofloxacin (Active Comparator) | Photosensitivity Index (PI) at 10 Minutes Under Condition 2 (i.e., Under UVA Exposure Only, Simulating Indoor Sun Exposure Behind Window Glass) | 1.03 Unitless |
Comparison: Mixed model for repeated measures (MMRM) with unstructured (UN) covariance matrix on photosensitivity index (PI) values90% CI: [-0.15, 0.36]Linear mixed model
p-value: 0.44690% CI: [-0.16, 0.36]Linear mixed model
p-value: 0.97290% CI: [-0.34, 0.35]Linear mixed model
Comparison: Mixed model for repeated measures (MMRM) with unstructured (UN) covariance matrix on photosensitivity index (PI) values90% CI: [-0.02, 0.6]Linear mixed model
p-value: 0.09190% CI: [-0.04, 0.56]Linear mixed model
p-value: 0.8890% CI: [-0.38, 0.44]Linear mixed model
Secondary
Photosensitivity Index (PI) at 1 Hour Under Condition 1 (i.e., Under Full Range of UVB/UVA Exposure, Simulating Midday Summer Outdoor Sun Exposure)
Photosensitivity index (PI) under condition 1 (C1)(i.e., under full range solar UVB/UVA (290 to 400 nm, UBV content \ 10%), simulating midday summer outdoor sun exposure (assessed in μw/cm2)), was defined as ratio of the precise Minimum erythema dose (MED)baseline to MEDon-drug at each respective post irradiation time point (i.e. 1 hour)(i.e., MEDon-drug\[millijoules (mJ)\]/MEDbaseline\[mJ\]) and was hence unitless. MED was defined as lowest dose that produced uniform redness (C1) (assessed in mJ for UVB/UVA). Subjects were exposed to a series of 6 graded full range solar UVB/UVA exposures, each 25% greater than the previous dose. Light exposure occurred 2 hours (±10 minutes) after dose on Day 8 of either investigational product (IP) or placebo, and on-treatment photosensitivity assessments (determination of MEDon-drug + evaluation of erythema/local skin reactions) were performed at 1 hour after irradiation.
Time frame: At 1 hour after irradiation on Day 8
Population: Full Analysis Set (FAS): This set included all subjects in the treated set (TS) who provided at least 1 photosensitivity endpoint that was defined as primary or secondary and was not excluded due to a protocol deviation relevant to the evaluation of photosensitivity.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo QD | Photosensitivity Index (PI) at 1 Hour Under Condition 1 (i.e., Under Full Range of UVB/UVA Exposure, Simulating Midday Summer Outdoor Sun Exposure) | 1.07 Unitless |
| 400 mg QD BI 730357 | Photosensitivity Index (PI) at 1 Hour Under Condition 1 (i.e., Under Full Range of UVB/UVA Exposure, Simulating Midday Summer Outdoor Sun Exposure) | 0.99 Unitless |
| Placebo BID | Photosensitivity Index (PI) at 1 Hour Under Condition 1 (i.e., Under Full Range of UVB/UVA Exposure, Simulating Midday Summer Outdoor Sun Exposure) | 1.04 Unitless |
| 300 mg BID BI 730357 | Photosensitivity Index (PI) at 1 Hour Under Condition 1 (i.e., Under Full Range of UVB/UVA Exposure, Simulating Midday Summer Outdoor Sun Exposure) | 1.08 Unitless |
| 500 mg Ciprofloxacin (Active Comparator) | Photosensitivity Index (PI) at 1 Hour Under Condition 1 (i.e., Under Full Range of UVB/UVA Exposure, Simulating Midday Summer Outdoor Sun Exposure) | 1.00 Unitless |
Comparison: Mixed model for repeated measures (MMRM) with unstructured (UN) covariance matrix on photosensitivity index (PI) values90% CI: [-0.15, -0.01]Linear mixed model
p-value: 0.75790% CI: [-0.09, 0.06]Linear mixed model
p-value: 0.15890% CI: [-0.17, 0.03]Linear mixed model
Comparison: Mixed model for repeated measures (MMRM) with unstructured (UN) covariance matrix on photosensitivity index (PI) values90% CI: [-0.12, 0.22]Linear mixed model
p-value: 0.3390% CI: [-0.09, 0.25]Linear mixed model
p-value: 0.75490% CI: [-0.26, 0.19]Linear mixed model
Secondary
Photosensitivity Index (PI) at 1 Hour Under Condition 2 (i.e., Under UVA Exposure Only, Simulating Indoor Sun Exposure Behind Window Glass)
Photosensitivity index (PI) under condition 2 (C2)(i.e., UVA only (320 to 400 nm, UVB content \<0.03%), simulating indoor exposure behind window glass with a secondary assessment of erythema and local skin reactions at 25 Joules centimetres-2 (J cm-2) (assessed in mw/cm2)), defined as ratio of precise Minimum erythema dose (MED)baseline to MEDon-drug at each respective post irradiation time point (i.e. 1 hour)(i.e. MEDon-drug\[Joules (J)\]/MEDbaseline\[J\]) and was hence unitless. MED defined as lowest dose that produced uniform darkening (C2) (assessed in J for UVA). Subjects were exposed to series of 6 graded full range solar UVA only exposures (C2), each 25% greater than the previous dose. Light exposure occurred 2 hours (±10 minutes) after dose on Day 8 of either investigational product (IP) or placebo, and on-treatment photosensitivity assessments (determination of MEDon-drug + evaluation of erythema/local skin reactions) were performed at 1 hour after irradiation.
Time frame: At 1 hour after irradiation on Day 8
Population: Full Analysis Set (FAS): This set included all subjects in the treated set (TS) who provided at least 1 photosensitivity endpoint that was defined as primary or secondary and was not excluded due to a protocol deviation relevant to the evaluation of photosensitivity.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo QD | Photosensitivity Index (PI) at 1 Hour Under Condition 2 (i.e., Under UVA Exposure Only, Simulating Indoor Sun Exposure Behind Window Glass) | 0.91 Unitless |
| 400 mg QD BI 730357 | Photosensitivity Index (PI) at 1 Hour Under Condition 2 (i.e., Under UVA Exposure Only, Simulating Indoor Sun Exposure Behind Window Glass) | 1.22 Unitless |
| Placebo BID | Photosensitivity Index (PI) at 1 Hour Under Condition 2 (i.e., Under UVA Exposure Only, Simulating Indoor Sun Exposure Behind Window Glass) | 1.00 Unitless |
| 300 mg BID BI 730357 | Photosensitivity Index (PI) at 1 Hour Under Condition 2 (i.e., Under UVA Exposure Only, Simulating Indoor Sun Exposure Behind Window Glass) | 1.19 Unitless |
| 500 mg Ciprofloxacin (Active Comparator) | Photosensitivity Index (PI) at 1 Hour Under Condition 2 (i.e., Under UVA Exposure Only, Simulating Indoor Sun Exposure Behind Window Glass) | 1.06 Unitless |
Comparison: Mixed model for repeated measures (MMRM) with unstructured (UN) covariance matrix on photosensitivity index (PI) values90% CI: [0.09, 0.52]Linear mixed model
p-value: 0.15190% CI: [-0.06, 0.38]Linear mixed model
p-value: 0.31990% CI: [-0.15, 0.44]Linear mixed model
Comparison: Mixed model for repeated measures (MMRM) with unstructured (UN) covariance matrix on photosensitivity index (PI) values90% CI: [-0.04, 0.42]Linear mixed model
p-value: 0.24690% CI: [-0.09, 0.36]Linear mixed model
p-value: 0.70490% CI: [-0.25, 0.36]Linear mixed model