Bioavailability, Pharmacokinetics, Safety
Conditions
Brief summary
This is a single-center, open-label, randomized, single dose, 3-way crossover study in healthy volunteers designed to evaluate the relative bioavailability of a new oral tablet formulation of linaprazan glurate in comparison to a previously studied oral tablet formulation under fasting conditions, and to assess the effect of a high fat, high calorie meal on the pharmacokinetics (PK) of linaprazan glurate and the active substance linaprazan after the administration of the new oral tablet formulation.
Interventions
100 mg
Sponsors
Cinclus Pharma Holding AB
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
Main Inclusion Criteria: 1. Willing and able to give written informed consent for participation in the study. 2. Healthy male or female aged 18 to 65 years, inclusive. 3. Body mass index ≥18.5 and ≤30.0 kg/m2. 4. Medically healthy, without abnormal clinically significant medical history 5. Female subjects of childbearing potential, as well as their partners and male subjects and their partners, who agree to using methods of contraception 6. Willing and able to consume the high-fat, high calorie breakfast
Exclusion criteria
1. Female subjects of childbearing potential unless they agree to use highly effective methods of contraception (failure rate of \<1%) from 2 weeks prior to dosing until the end-of-study visit. 2. Male subjects with a partner of childbearing potential, unless they agree to use method of contraception from 2 weeks prior to dosing until the end-of-study visit.History of or current clinically significant disease as defined in the protocol 3. History of or current clinically significant disease as defined in the protocol. 4. History of GERD, significant acid reflux. 5. Subjects who are pregnant, currently breastfeeding, or intend to become pregnant (female subjects) or father a child (male subjects) during the course of the study (i.e., from screening to end of study visit).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Relative Bioavailability of Linaprazan Test Formulation in Fed vs. Fasting Conditions, Based on the Means Ratios for Cmax | From pre-dose up to 72 h post dose | The Ratio of Cmax of linaprazan when comparing test formulation vs reference formulation (treatments C vs treatment B), i.e. how much linaprazan exposure is increased or decreased with the new formulation. |
| Relative Bioavailability of Linaprazan Comparing Test Formulation vs. Reference Formulation of Linaprazan Glurate. Ratios of AUCinf and AUClast | From pre-dose up to 72 h post dose | The Ratio of Area Under the plasma concentration vs. time Curve (AUC) from time 0 to infinity (AUCinf), and from time 0 to last measurement (AUClast) of linaprazan, comparing test formulation vs reference formulation (treatments B vs treatment A) for Relative Bioavailability, i.e. how much linaprazan exposure is increased or decreased with the new formulation. |
| Relative Bioavailability of Linaprazan Comparing Test Formulation vs. Reference Formulation of Linaprazan Glurate. Ratio of Cmax | From pre-dose up to 72 h post dose | The Ratio of Cmax (highest measured concentration) of linaprazan comparing the test formulation vs reference formulation (treatments B vs treatment A) for Relative Bioavailability, i.e. how much linaprazan exposure is increased or decreased with the new formulation. |
| Relative Bioavailability of Linaprazan Test Formulation in Fed vs. Fasting Conditions, Based on the Means Ratios for AUCinf and AUClast | From pre-dose up to 72 h post dose | The Ratio of Area Under the plasma concentration vs. time Curve (AUC) from time 0 to infinity (AUCinf), and from time 0 to last measurement (AUClast) of linaprazan, comparing test formulation vs reference formulation (treatments C vs treatment B) for Relative Bioavailability, i.e. how much linaprazan exposure is increased or decreased in a fed vs fasted state. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Relative Bioavailability of Linaprazan Glurate for the Test Formulation vs. Reference Formulation of Linaprazan Glurate, Based on the Means Ratios of PK Parameters. | From pre-dose up to 72 h post dose | The Ratio of Area Under the plasma concentration vs. time Curve (AUC) from time 0 to infinity (AUCinf), and from time 0 to last measurement (AUClast) of linaprzan glurate, comparing test formulation vs reference formulation (treatments B vs treatment A) for Relative Bioavailability, i.e. how much linaprazan glurate exposure is increased or decreased with the new formulation. |
| Relative Bioavailability of Linaprazan Glurate Comparing Test Formulation vs. Reference Formulation of Linaprazan Glurate. Ratio of Cmax | From pre-dose up to 72 h post dose | The Ratio of Cmax (highest measured concentration) of linaprazan glurate comparing the test formulation vs reference formulation (treatments B vs treatment A) for Relative Bioavailability, i.e. how much linaprazan glurate exposure is increased or decreased with the new formulation. |
| Relative Bioavailability of Linaprazan Glurate in Fed vs. Fasting Conditions, Based on the Means Ratios for AUCinf, AUClast | From pre-dose up to 72 h post dose | The Ratio of Area Under the plasma concentration vs. time Curve (AUC) from time 0 to infinity (AUCinf), and from time 0 to last measurement (AUClast) of linaprazan glurate, comparing test formulation vs reference formulation (treatments C vs treatment B) for Relative Bioavailability, i.e. how much linaprazan glurate exposure is increased or decreased in a fed vs fasted state. |
| Relative Bioavailability of Linaprazan Glurate in Fed vs. Fasting Conditions, Based on the Means Ratio of Cmax | From pre-dose up to 72 h post dose | The Ratio of Cmax of linaprazan glurate when comparing test formulation vs reference formulation (treatments C vs treatment B), i.e. how much linaprazan glurate exposure is increased or decreased with the new formulation. |
Countries
Slovenia
Participant flow
Recruitment details
Subjects were recruited form CRS's database of healthy volunteers. All Volunteers were recruited in Slovenia, Ljubljana.
Pre-assignment details
Approximately 84 healthy volunteers were planned to be screened to achieve 54 randomized subjects. 97 Volunteers were actually screened for eligibility, of those, 67 were Randomized and 49 Analyzed.
Participants by arm
| Arm | Count |
|---|---|
| Treatment Sequence A B C Treatments A = 100 mg reference formulation non-fasted B = 100 mg test formualtion non-fasted C = 100 mg test formulation fasted | 15 |
| Treatment A C B Treatments A = 100 mg reference formulation non-fasted B = 100 mg test formualtion non-fasted C = 100 mg test formulation fasted | 15 |
| Treatment B A C Treatments A = 100 mg reference formulation non-fasted B = 100 mg test formualtion non-fasted C = 100 mg test formulation fasted | 9 |
| Treatment B C A Treatments A = 100 mg reference formulation non-fasted B = 100 mg test formualtion non-fasted C = 100 mg test formulation fasted | 10 |
| Treatment C A B Treatments A = 100 mg reference formulation non-fasted B = 100 mg test formualtion non-fasted C = 100 mg test formulation fasted | 9 |
| Treatment C B A Treatments A = 100 mg reference formulation non-fasted B = 100 mg test formualtion non-fasted C = 100 mg test formulation fasted | 9 |
| Total | 67 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 |
|---|---|---|---|---|---|---|---|---|---|
| Treatment Period 1 | Adverse Event | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 1 |
| Treatment Period 1 | Protocol Violation | 0 | 0 | 0 | 0 | 0 | 0 | 6 | 6 |
| Treatment Period 1 | Withdrawal by Subject | 0 | 0 | 1 | 0 | 0 | 1 | 0 | 0 |
| Treatment Period 2 | Adverse Event | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Treatment Period 2 | Withdrawal by Subject | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | Treatment Sequence A B C | Treatment A C B | Treatment B A C | Treatment B C A | Treatment C A B | Treatment C B A | Total |
|---|---|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 15 Participants | 15 Participants | 9 Participants | 10 Participants | 9 Participants | 9 Participants | 67 Participants |
| Age, Continuous | 22.2 years | 24.3 years | 26.4 years | 21.5 years | 29.6 years | 22.3 years | 24.1 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 14 Participants | 15 Participants | 9 Participants | 10 Participants | 9 Participants | 9 Participants | 66 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Region of Enrollment Slovenia | 15 participants | 15 participants | 9 participants | 10 participants | 9 participants | 9 participants | 67 participants |
| Sex: Female, Male Female | 7 Participants | 9 Participants | 8 Participants | 2 Participants | 6 Participants | 3 Participants | 35 Participants |
| Sex: Female, Male Male | 8 Participants | 6 Participants | 1 Participants | 8 Participants | 3 Participants | 6 Participants | 32 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 / 51 | 0 / 53 | 0 / 50 | 0 / 13 |
| other Total, other adverse events | 17 / 51 | 12 / 53 | 14 / 50 | 4 / 13 |
| serious Total, serious adverse events | 0 / 51 | 1 / 53 | 0 / 50 | 0 / 13 |
Outcome results
Primary
Relative Bioavailability of Linaprazan Comparing Test Formulation vs. Reference Formulation of Linaprazan Glurate. Ratio of Cmax
The Ratio of Cmax (highest measured concentration) of linaprazan comparing the test formulation vs reference formulation (treatments B vs treatment A) for Relative Bioavailability, i.e. how much linaprazan exposure is increased or decreased with the new formulation.
Time frame: From pre-dose up to 72 h post dose
Population: PK analysis set
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Reference Formulation (Treatment A) | Relative Bioavailability of Linaprazan Comparing Test Formulation vs. Reference Formulation of Linaprazan Glurate. Ratio of Cmax | 1430 nmol/L | Standard Deviation 1.83 |
| Test Formulation (Treatment B) | Relative Bioavailability of Linaprazan Comparing Test Formulation vs. Reference Formulation of Linaprazan Glurate. Ratio of Cmax | 3462.2 nmol/L | Standard Deviation 1.25 |
Comparison: Ratio of geometric mean Cmax comparing test formulation fasted (treatment B) vs. reference formulation fasted (treatment A). This is a relative comparison, thus there is no unit. The ratio is given under the Estimated value.p-value: <0.000195% CI: [2.0922, 2.5652]Mixed Models Analysis
Primary
Relative Bioavailability of Linaprazan Comparing Test Formulation vs. Reference Formulation of Linaprazan Glurate. Ratios of AUCinf and AUClast
The Ratio of Area Under the plasma concentration vs. time Curve (AUC) from time 0 to infinity (AUCinf), and from time 0 to last measurement (AUClast) of linaprazan, comparing test formulation vs reference formulation (treatments B vs treatment A) for Relative Bioavailability, i.e. how much linaprazan exposure is increased or decreased with the new formulation.
Time frame: From pre-dose up to 72 h post dose
Population: PK Analysis Set
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Reference Formulation (Treatment A) | Relative Bioavailability of Linaprazan Comparing Test Formulation vs. Reference Formulation of Linaprazan Glurate. Ratios of AUCinf and AUClast | AUCinf | 12341 hours * nmol/Liter | Standard Deviation 1.51 |
| Reference Formulation (Treatment A) | Relative Bioavailability of Linaprazan Comparing Test Formulation vs. Reference Formulation of Linaprazan Glurate. Ratios of AUCinf and AUClast | AUClast | 10016.2 hours * nmol/Liter | Standard Deviation 2.78 |
| Test Formulation (Treatment B) | Relative Bioavailability of Linaprazan Comparing Test Formulation vs. Reference Formulation of Linaprazan Glurate. Ratios of AUCinf and AUClast | AUCinf | 25001 hours * nmol/Liter | Standard Deviation 1.32 |
| Test Formulation (Treatment B) | Relative Bioavailability of Linaprazan Comparing Test Formulation vs. Reference Formulation of Linaprazan Glurate. Ratios of AUCinf and AUClast | AUClast | 24175.8 hours * nmol/Liter | Standard Deviation 1.34 |
Comparison: The Ratio of geometric mean AUCinf comparing test formulation fasted (treatment B) vs. reference formulation fasted ( treatment A). This is a relative comparison, thus there is no unit. The ratio is given under the Estimated value.p-value: <0.000195% CI: [1.8399, 2.1641]Mixed Models Analysis
Comparison: AUClast: Ratio of geometric mean AUClast comparing test formulation fasted (treatment B) vs. reference formulation fasted (treatment A). This is a relative comparison, thus there is no unit. The ratio is given under the Estimated value.p-value: <0.000195% CI: [1.9664, 2.2963]Mixed Models Analysis
Primary
Relative Bioavailability of Linaprazan Test Formulation in Fed vs. Fasting Conditions, Based on the Means Ratios for AUCinf and AUClast
The Ratio of Area Under the plasma concentration vs. time Curve (AUC) from time 0 to infinity (AUCinf), and from time 0 to last measurement (AUClast) of linaprazan, comparing test formulation vs reference formulation (treatments C vs treatment B) for Relative Bioavailability, i.e. how much linaprazan exposure is increased or decreased in a fed vs fasted state.
Time frame: From pre-dose up to 72 h post dose
Population: PK Analysis Set.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Reference Formulation (Treatment A) | Relative Bioavailability of Linaprazan Test Formulation in Fed vs. Fasting Conditions, Based on the Means Ratios for AUCinf and AUClast | AUCinf | 25001 hours * nmol/Liter | Standard Deviation 1.32 |
| Reference Formulation (Treatment A) | Relative Bioavailability of Linaprazan Test Formulation in Fed vs. Fasting Conditions, Based on the Means Ratios for AUCinf and AUClast | AUClast | 24175.8 hours * nmol/Liter | Standard Deviation 1.34 |
| Test Formulation (Treatment B) | Relative Bioavailability of Linaprazan Test Formulation in Fed vs. Fasting Conditions, Based on the Means Ratios for AUCinf and AUClast | AUCinf | 19448.9 hours * nmol/Liter | Standard Deviation 1.32 |
| Test Formulation (Treatment B) | Relative Bioavailability of Linaprazan Test Formulation in Fed vs. Fasting Conditions, Based on the Means Ratios for AUCinf and AUClast | AUClast | 19022.8 hours * nmol/Liter | Standard Deviation 1.32 |
Comparison: Ratio of geometric mean AUCinf comparing treatment C (fed) versus treatment B (fasted). This is a relative comparison, thus there is no unit. The ratio is given under the Estimated value.p-value: <0.000195% CI: [0.7009, 0.8177]Mixed Models Analysis
Comparison: Ratio of geometric mean AUClast comparing treatment C (fed) versus treatment B (fasted). This is a relative comparison, thus there is no unit. The ratio is given under the Estimated value.p-value: <0.000195% CI: [0.7102, 0.8313]Mixed Models Analysis
Primary
Relative Bioavailability of Linaprazan Test Formulation in Fed vs. Fasting Conditions, Based on the Means Ratios for Cmax
The Ratio of Cmax of linaprazan when comparing test formulation vs reference formulation (treatments C vs treatment B), i.e. how much linaprazan exposure is increased or decreased with the new formulation.
Time frame: From pre-dose up to 72 h post dose
Population: PK analysis set
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Reference Formulation (Treatment A) | Relative Bioavailability of Linaprazan Test Formulation in Fed vs. Fasting Conditions, Based on the Means Ratios for Cmax | 3462.2 nmol/L | Standard Deviation 1.25 |
| Test Formulation (Treatment B) | Relative Bioavailability of Linaprazan Test Formulation in Fed vs. Fasting Conditions, Based on the Means Ratios for Cmax | 1608 nmol/L | Standard Deviation 1.29 |
Comparison: Ratio of geometric mean Cmax comparing treatment C (fed) versus treatment B (fasted). This is a relative comparison, thus there is no unit. The ratio is given under the Estimated value.p-value: <0.000195% CI: [0.1999, 0.3247]Mixed Models Analysis
Secondary
Relative Bioavailability of Linaprazan Glurate Comparing Test Formulation vs. Reference Formulation of Linaprazan Glurate. Ratio of Cmax
The Ratio of Cmax (highest measured concentration) of linaprazan glurate comparing the test formulation vs reference formulation (treatments B vs treatment A) for Relative Bioavailability, i.e. how much linaprazan glurate exposure is increased or decreased with the new formulation.
Time frame: From pre-dose up to 72 h post dose
Population: PK Analysis Set
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Reference Formulation (Treatment A) | Relative Bioavailability of Linaprazan Glurate Comparing Test Formulation vs. Reference Formulation of Linaprazan Glurate. Ratio of Cmax | 86.8 nmol/L | Standard Deviation 2.44 |
| Test Formulation (Treatment B) | Relative Bioavailability of Linaprazan Glurate Comparing Test Formulation vs. Reference Formulation of Linaprazan Glurate. Ratio of Cmax | 214.3 nmol/L | Standard Deviation 2.08 |
Comparison: Ratio of geometric mean Cmax comparing test formulation fasted (treatment B) vs. reference formulation fasted ( treatment A). This is a relative comparison, thus there is no unit. The ratio is given under the Estimated value.p-value: <0.000195% CI: [2.5098, 3.6446]Mixed Models Analysis
Secondary
Relative Bioavailability of Linaprazan Glurate for the Test Formulation vs. Reference Formulation of Linaprazan Glurate, Based on the Means Ratios of PK Parameters.
The Ratio of Area Under the plasma concentration vs. time Curve (AUC) from time 0 to infinity (AUCinf), and from time 0 to last measurement (AUClast) of linaprzan glurate, comparing test formulation vs reference formulation (treatments B vs treatment A) for Relative Bioavailability, i.e. how much linaprazan glurate exposure is increased or decreased with the new formulation.
Time frame: From pre-dose up to 72 h post dose
Population: PK Analysis Set
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Reference Formulation (Treatment A) | Relative Bioavailability of Linaprazan Glurate for the Test Formulation vs. Reference Formulation of Linaprazan Glurate, Based on the Means Ratios of PK Parameters. | AUCinf | 114.2 hours * nmol/Liter | Standard Deviation 1.95 |
| Reference Formulation (Treatment A) | Relative Bioavailability of Linaprazan Glurate for the Test Formulation vs. Reference Formulation of Linaprazan Glurate, Based on the Means Ratios of PK Parameters. | AUClast | 83.9 hours * nmol/Liter | Standard Deviation 2.49 |
| Test Formulation (Treatment B) | Relative Bioavailability of Linaprazan Glurate for the Test Formulation vs. Reference Formulation of Linaprazan Glurate, Based on the Means Ratios of PK Parameters. | AUCinf | 320.2 hours * nmol/Liter | Standard Deviation 1.73 |
| Test Formulation (Treatment B) | Relative Bioavailability of Linaprazan Glurate for the Test Formulation vs. Reference Formulation of Linaprazan Glurate, Based on the Means Ratios of PK Parameters. | AUClast | 293 hours * nmol/Liter | Standard Deviation 1.84 |
Comparison: Ratio of geometric mean AUCinf comparing test formulation fasted (treatment B) vs. reference formulation fasted ( treatment A). This is a relative comparison, thus there is no unit. The ratio is given under the Estimated value.p-value: <0.000195% CI: [2.5098, 3.6446]Mixed Models Analysis
Comparison: Ratio of geometric mean AUClast comparing test formulation fasted (treatment B) vs. reference formulation fasted (treatment A). This is a relative comparison, thus there is no unit. The ratio is given under the Estimated value.p-value: <0.000195% CI: [2.9076, 4.2799]Mixed Models Analysis
Secondary
Relative Bioavailability of Linaprazan Glurate in Fed vs. Fasting Conditions, Based on the Means Ratio of Cmax
The Ratio of Cmax of linaprazan glurate when comparing test formulation vs reference formulation (treatments C vs treatment B), i.e. how much linaprazan glurate exposure is increased or decreased with the new formulation.
Time frame: From pre-dose up to 72 h post dose
Population: PK Analysis Set.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Reference Formulation (Treatment A) | Relative Bioavailability of Linaprazan Glurate in Fed vs. Fasting Conditions, Based on the Means Ratio of Cmax | 214.3 nmol/L | Standard Deviation 2.08 |
| Test Formulation (Treatment B) | Relative Bioavailability of Linaprazan Glurate in Fed vs. Fasting Conditions, Based on the Means Ratio of Cmax | 55.0 nmol/L | Standard Deviation 2.23 |
Comparison: Ratio of geometric mean Cmax comparing test formulation fed (treatment C) vs. reference formulation fasted (treatment B). This is a relative comparison, thus there is no unit. The ratio is given under the Estimated value.p-value: <0.000195% CI: [0.198, 0.3211]Mixed Models Analysis
Secondary
Relative Bioavailability of Linaprazan Glurate in Fed vs. Fasting Conditions, Based on the Means Ratios for AUCinf, AUClast
The Ratio of Area Under the plasma concentration vs. time Curve (AUC) from time 0 to infinity (AUCinf), and from time 0 to last measurement (AUClast) of linaprazan glurate, comparing test formulation vs reference formulation (treatments C vs treatment B) for Relative Bioavailability, i.e. how much linaprazan glurate exposure is increased or decreased in a fed vs fasted state.
Time frame: From pre-dose up to 72 h post dose
Population: PK Analysis Set.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Reference Formulation (Treatment A) | Relative Bioavailability of Linaprazan Glurate in Fed vs. Fasting Conditions, Based on the Means Ratios for AUCinf, AUClast | AUCinf | 320.2 hours * nmol/Liter | Standard Deviation 1.73 |
| Reference Formulation (Treatment A) | Relative Bioavailability of Linaprazan Glurate in Fed vs. Fasting Conditions, Based on the Means Ratios for AUCinf, AUClast | AUClast | 293.0 hours * nmol/Liter | Standard Deviation 1.84 |
| Test Formulation (Treatment B) | Relative Bioavailability of Linaprazan Glurate in Fed vs. Fasting Conditions, Based on the Means Ratios for AUCinf, AUClast | AUClast | 144.3 hours * nmol/Liter | Standard Deviation 1.62 |
| Test Formulation (Treatment B) | Relative Bioavailability of Linaprazan Glurate in Fed vs. Fasting Conditions, Based on the Means Ratios for AUCinf, AUClast | AUCinf | 166.3 hours * nmol/Liter | Standard Deviation 1.52 |
Comparison: Ratio of geometric mean AUCinf comparing treatment C (fed) versus treatment B (fasted). This is a relative comparison, thus there is no unit. The ratio is given under the Estimated value.p-value: <0.000195% CI: [0.4131, 0.5867]Mixed Models Analysis
Comparison: Ratio of geometric mean AUClast comparing treatment C (fed) versus treatment B (fasted). This is a relative comparison, thus there is no unit. The ratio is given under the Estimated value.p-value: <0.000195% CI: [0.4047, 0.5989]Mixed Models Analysis