A Phase 1 interventional study of PF-07081532 in Type 2 Diabetes and Renal Impairment, sponsored by Pfizer. Terminated at 2 sites in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2024-11-05.
Sponsored by Pfizer · Phase 1, Interventional, and Basic science
The purpose of this study is to understand the effects of kidney functional impairment may have on the study medicine (PF-07081532). People with certain level of kidney functional impairment may process PF-07081532 differently from healthy people. PF-07081532 is developed as a potential treatment for type II diabetes.
Participants will take the study medicine as a tablet by mouth once at the study clinic and then will stay at the study clinic for about 7 days. During that time, the study team will monitor their treatment experience and take some blood samples to test the level of PF-07081532. This will help us understand if certain degree of kidney functional impairment will have an effect on the study medicine PF-07081532.
9,589 studies on the registry are indexed under Diabetes Mellitus, Type 2; 1,332 are open to participants now.
This study's enrollment of 18 is below the median of 81 across 7,713 interventional studies indexed under Diabetes Mellitus, Type 2.
Browse Diabetes Mellitus, Type 2 studies →Pfizer is the lead sponsor of 3,323 studies on the registry; 145 are open to participants now.
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NORMAL FUNCTION (GROUP 1): Normal renal function (mean eGFR ≥90 mL/min) based on an average of measures from Screening visits S1 and S2 (eGFR should be calculated using the 2021 CKD EPI Scr-Scys combined equation:
Exclusion Criteria:
Participants without renal impairment will receive a single 20 mg dose of PF 07081532, administered orally
Drug: PF-07081532
Participants with mild renal impairment will receive a single 20 mg dose of PF 07081532, administered orally
Drug: PF-07081532
Participants with moderate renal impairment will receive a single 20 mg dose of PF 07081532, administered orally
Drug: PF-07081532
Participants with severe renal impairment will receive a single 20 mg dose of PF 07081532, administered orally
Drug: PF-07081532
One PF-07081532 20 mg tablet, administered orally
Maximum Observed Concentration (Cmax) for PF-07081532 Following a Single Oral Dose of PF-07081532 20 mg in Participants With Varying Degrees of Renal Impairment
Plasma Cmax was observed directly from data.
Time frame: Pre-dose, 0.5, 1, 2, 4, 6, 8, 10, 12, 15, 24, 36, 48, 72, 96, 120, 144 hours post dose on Day 1
Unbound Cmax (Cmax,u) for PF-07081532 Following a Single Oral Dose of PF-07081532 20 mg in Participants With Varying Degrees of Renal Impairment
Cmax,u was calculated as fu\*Cmax. Plasma Cmax was observed directly from data. fu was defined as the fraction of unbound drug in plasma, and was obtained from measurement of protein binding.
Time frame: Pre-dose, 0.5, 1, 2, 4, 6, 8, 10, 12, 15, 24, 36, 48, 72, 96, 120, 144 hours post dose on Day 1
Area Under the Concentration-Time Curve From Time 0 to Infinity (AUCinf) for PF-07081532 Following a Single Oral Dose of PF-07081532 20 mg in Participants With Varying Degrees of Renal Impairment
AUCinf was calculated as AUClast + (Clast\*/kel). AUClast was defined as area under the plasma concentration-time profile from time 0 to the time last measurable concentration, and was calculated using linear/log trapezoidal method. Clast\* was defined as the predicted plasma concentration at the last quantifiable time point estimated from log-linear regression analysis. kel was the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve.
Time frame: Pre-dose, 0.5, 1, 2, 4, 6, 8, 10, 12, 15, 24, 36, 48, 72, 96, 120, 144 hours post dose on Day 1
Unbound AUCinf (AUCinf,u) for PF-07081532 Following a Single Oral Dose of PF-07081532 20 mg in Participants With Varying Degrees of Renal Impairment
AUCinf,u was calculated as fu\*AUCinf. AUCinf was calculated as AUClast + (Clast\*/kel). AUClast was defined as area under the plasma concentration-time profile from time 0 to the time last measurable concentration, and was calculated using linear/log trapezoidal method. Clast\* was defined as the predicted plasma concentration at the last quantifiable time point estimated from log-linear regression analysis. kel was the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve. fu was the fraction of unbound drug in plasma, and was obtained from measurement of protein binding.
Time frame: Pre-dose, 0.5, 1, 2, 4, 6, 8, 10, 12, 15, 24, 36, 48, 72, 96, 120, 144 hours post dose on Day 1
Unbound Fraction (fu) for PF-07081532 Following a Single Oral Dose of PF-07081532 20 mg in Participants With Varying Degrees of Renal Impairment
fu was the ratio of unbound drug concentration to the total drug concentration, and was obtained from measurement of protein binding.
Time frame: Pre-dose, 0.5, 1, 2, 4, 6, 8, 10, 12, 15, 24, 36, 48, 72, 96, 120, 144 hours post dose on Day 1
Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
An adverse event (AE) was any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. Treatment-related AE was any untoward medical occurrence attributed to study treatment in a participant who received study treatment. Treatment-emergent AEs (TEAEs) = AEs occurred after starting of study treatment and up to the end of study that were absent before treatment or that worsened relative to pretreatment state. A serious AE (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-related AEs and SAEs were determined by the investigator. Severe=an event that prevents normal everyday activities.
Time frame: From time of administration of study treatment on Day 1 up to the end of the study (up to a maximum of 31 days post dose)
Number of Participants With Laboratory Test Abnormalities
Parameters analyzed for lab examination included hematology (hemoglobin, hematocrit, red blood cell count, mean corpuscular volume, mean corpuscular hemoglobin \[MCH\], MCH concentration, platelet count, white blood cell count, absolute \[Abs\] total neutrophils, Abs eosinophils, Abs monocytes, Abs basophils, Abs lymphocytes), chemistry (Scr, Scys, fasting plasma glucose, calcium, sodium, potassium, chloride, magnesium, phosphate, total bicarbonate, aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, gamma glutamyl eGFR), urinalysis (pH, qualitative \[qual\] glucose, qual protein, qual blood, ketones, nitrites, leukocyte, esterase, urobilinogen, urine bili, microscopy). Lab parameters meeting the predefined criteria and with at least 1 occurrence from baseline up to end of study are reported. Baseline was defined as the last pre-dose measurement.
Time frame: Pre-dose, 72 and 144 hours post dose on Day 1
Number of Participants With Vital Signs Data Meeting Pre-Defined Categorical Criteria
Vital signs including single, seated blood pressure (BP) and pulse rate were measured with the participant's arm supported at the level of the heart, and recorded to the nearest mmHg, following a seated rest of ≥5 minutes. Same arm (preferably the dominant arm) was used for BP/pulse rate assessment throughout the study. Vital signs meeting the predefined criteria and with at least 1 occurrence from baseline up to end of study are reported. Baseline was defined as the last pre-dose measurement.
Time frame: At admission on Day -1, pre-dose, and 24, 72, and 144 hours post the dose on Day 1
Number of Participants With Electrocardiogram (ECG) Data Meeting Pre-Defined Categorical Criteria
Supine standard 12-lead ECGs utilizing limb leads (with a 10-second rhythm strip) were collected at times specified in the time frame using an ECG machine that automatically calculates the HR and measures PR interval, QT interval, QTcF, and QRS complex. All scheduled ECGs were performed after the participant had rested quietly for at least 5 minutes in a supine position. ECG data meeting the predefined criteria and with at least 1 occurrence from baseline up to end of study were reported. Baseline was defined as the last pre-dose measurement.
Time frame: Pre-dose, and 144 hours post the dose on Day 1
The study was terminated due to the termination of clinical development of PF-07081532. As of the last participant last visit (LPLV) date (20 Jul 2023), a total of 18 participants were enrolled at 2 sites in the United States, and no participants without renal impairment were enrolled due to early study termination.
| Milestone | Mild Renal Impairment | Moderate Renal Impairment | Severe Renal Impairment |
|---|---|---|---|
| Started | 5 | 5 | 8 |
| Completed | 4 | 5 | 8 |
| Not completed | 1 | 0 | 0 |
| Withdrew: Withdrawal by subject | 1 | 0 | 0 |
Plasma Cmax was observed directly from data.
| Nanograms per milliliter (ng/mL) | Mild Renal Impairment | Moderate Renal Impairment | Severe Renal Impairment |
|---|---|---|---|
| Maximum Observed Concentration (Cmax) for PF-07081532 Following a Single Oral Dose of PF-07081532 20 mg in Participants With Varying Degrees of Renal Impairment | 2084 ± 50 | 1823 ± 24 | 1978 ± 30 |
Cmax,u was calculated as fu\*Cmax. Plasma Cmax was observed directly from data. fu was defined as the fraction of unbound drug in plasma, and was obtained from measurement of protein binding.
| ng/mL | Mild Renal Impairment | Moderate Renal Impairment | Severe Renal Impairment |
|---|---|---|---|
| Unbound Cmax (Cmax,u) for PF-07081532 Following a Single Oral Dose of PF-07081532 20 mg in Participants With Varying Degrees of Renal Impairment | 0.6178 ± 44 | 0.5895 ± 17 | 0.8239 ± 27 |
AUCinf was calculated as AUClast + (Clast\*/kel). AUClast was defined as area under the plasma concentration-time profile from time 0 to the time last measurable concentration, and was calculated using linear/log trapezoidal method. Clast\* was defined as the predicted plasma concentration at the last quantifiable time point estimated from log-linear regression analysis. kel was the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve.
| Nanograms*hours/milliliter (ng*h/mL) | Mild Renal Impairment | Moderate Renal Impairment | Severe Renal Impairment |
|---|---|---|---|
| Area Under the Concentration-Time Curve From Time 0 to Infinity (AUCinf) for PF-07081532 Following a Single Oral Dose of PF-07081532 20 mg in Participants With Varying Degrees of Renal Impairment | 59820 ± 41 | 45600 ± 21 | 43870 ± 33 |
AUCinf,u was calculated as fu\*AUCinf. AUCinf was calculated as AUClast + (Clast\*/kel). AUClast was defined as area under the plasma concentration-time profile from time 0 to the time last measurable concentration, and was calculated using linear/log trapezoidal method. Clast\* was defined as the predicted plasma concentration at the last quantifiable time point estimated from log-linear regression analysis. kel was the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve. fu was the fraction of unbound drug in plasma, and was obtained from measurement of protein binding.
| ng*h/mL | Mild Renal Impairment | Moderate Renal Impairment | Severe Renal Impairment |
|---|---|---|---|
| Unbound AUCinf (AUCinf,u) for PF-07081532 Following a Single Oral Dose of PF-07081532 20 mg in Participants With Varying Degrees of Renal Impairment | 17.51 ± 56 | 14.75 ± 31 | 18.44 ± 35 |
fu was the ratio of unbound drug concentration to the total drug concentration, and was obtained from measurement of protein binding.
| Ratio | Mild Renal Impairment | Moderate Renal Impairment | Severe Renal Impairment |
|---|---|---|---|
| Unbound Fraction (fu) for PF-07081532 Following a Single Oral Dose of PF-07081532 20 mg in Participants With Varying Degrees of Renal Impairment | 0.0002964 ± 14 | 0.0003234 ± 15 | 0.0004163 ± 15 |
An adverse event (AE) was any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. Treatment-related AE was any untoward medical occurrence attributed to study treatment in a participant who received study treatment. Treatment-emergent AEs (TEAEs) = AEs occurred after starting of study treatment and up to the end of study that were absent before treatment or that worsened relative to pretreatment state. A serious AE (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-related AEs and SAEs were determined by the investigator. Severe=an event that prevents normal everyday activities.
| Participants | Mild Renal Impairment | Moderate Renal Impairment | Severe Renal Impairment |
|---|---|---|---|
| Participants With All-Causality TEAEs | 1 | 2 | 1 |
| Participants With All-Causality SAEs | 0 | 0 | 0 |
| Participants With All-Causality Severe TEAEs | 0 | 0 | 0 |
| Participants With Treatment-Related TEAEs | 0 | 2 | 0 |
| Participants With Treatment-Related SAEs | 0 | 0 | 0 |
| Participants With Treatment-Related Severe TEAEs | 0 | 0 | 0 |
Parameters analyzed for lab examination included hematology (hemoglobin, hematocrit, red blood cell count, mean corpuscular volume, mean corpuscular hemoglobin \[MCH\], MCH concentration, platelet count, white blood cell count, absolute \[Abs\] total neutrophils, Abs eosinophils, Abs monocytes, Abs basophils, Abs lymphocytes), chemistry (Scr, Scys, fasting plasma glucose, calcium, sodium, potassium, chloride, magnesium, phosphate, total bicarbonate, aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, gamma glutamyl eGFR), urinalysis (pH, qualitative \[qual\] glucose, qual protein, qual blood, ketones, nitrites, leukocyte, esterase, urobilinogen, urine bili, microscopy). Lab parameters meeting the predefined criteria and with at least 1 occurrence from baseline up to end of study are reported. Baseline was defined as the last pre-dose measurement.
| Participants | Mild Renal Impairment | Moderate Renal Impairment | Severe Renal Impairment |
|---|---|---|---|
| Hematology-Hemoglobin (grams per deciliter [g/dL])<0.8*lower limit of normal (LLN) | 0 | 1 | 4 |
| Hematology-Hematocrit (%)<0.8*LLN | 0 | 0 | 4 |
| Hematology-Erythrocytes (10^12/Liter [L])<0.8*LLN | 0 | 1 | 4 |
| Hematology-Eosinophils (10^9/L)>1.2* upper limit of normal (ULN) | 0 | 0 | 1 |
| Clinical Chemistry-Gamma Glutamyl Transferase (units [U]/L)>3.0*ULN | 0 | 0 | 1 |
| Clinical Chemistry-Urea Nitrogen (milligrams [mg] / dL)>1.3*ULN | 1 | 4 | 7 |
| Clinical Chemistry-Creatinine (mg/dL)>1.3*ULN | 0 | 3 | 8 |
| Clinical Chemistry-Urate (mg/dL)>1.2*ULN | 0 | 0 | 1 |
| Clinical Chemistry-Potassium (milliequivalents [mEq] / L)>1.1*ULN | 0 | 0 | 1 |
| Clinical Chemistry-Magnesium (mg/dL)<0.9*LLN | 0 | 1 | 0 |
| Clinical Chemistry-Phosphate (mg/dL)<0.8*LLN | 0 | 0 | 1 |
| Clinical Chemistry-Phosphate (mg/dL)>1.2*ULN | 0 | 1 | 0 |
| Clinical Chemistry-Bicarbonate (mEq/L)<0.9*LLN | 0 | 0 | 1 |
| Clinical Chemistry-Fasting Glucose (mg/dL)>1.5*ULN | 1 | 3 | 2 |
| Urinalysis-Urine Glucose Positive | 0 | 1 | 1 |
| Urinalysis-Urine Protein Positive | 0 | 2 | 5 |
| Urinalysis-Urine Hemoglobin Positive | 0 | 0 | 1 |
| Urinalysis-Nitrite Positive | 1 | 0 | 1 |
| Urinalysis-Leukocyte Esterase Positive | 1 | 1 | 2 |
Vital signs including single, seated blood pressure (BP) and pulse rate were measured with the participant's arm supported at the level of the heart, and recorded to the nearest mmHg, following a seated rest of ≥5 minutes. Same arm (preferably the dominant arm) was used for BP/pulse rate assessment throughout the study. Vital signs meeting the predefined criteria and with at least 1 occurrence from baseline up to end of study are reported. Baseline was defined as the last pre-dose measurement.
| Participants | Mild Renal Impairment | Moderate Renal Impairment | Severe Renal Impairment |
|---|---|---|---|
| Systolic BP (mm Hg) Increase >=30 mm Hg | 0 | 1 | 1 |
| Diastolic BP (mm Hg) Increase >=20 mm Hg | 0 | 0 | 1 |
| Diastolic BP (mm Hg) Decrease >=20 mm Hg | 0 | 0 | 1 |
Supine standard 12-lead ECGs utilizing limb leads (with a 10-second rhythm strip) were collected at times specified in the time frame using an ECG machine that automatically calculates the HR and measures PR interval, QT interval, QTcF, and QRS complex. All scheduled ECGs were performed after the participant had rested quietly for at least 5 minutes in a supine position. ECG data meeting the predefined criteria and with at least 1 occurrence from baseline up to end of study were reported. Baseline was defined as the last pre-dose measurement.
| Participants | Mild Renal Impairment | Moderate Renal Impairment | Severe Renal Impairment |
|---|---|---|---|
| Number of Participants With Electrocardiogram (ECG) Data Meeting Pre-Defined Categorical Criteria | 1 | 1 | 2 |
Collected over From time of administration of study treatment on Day 1 up to the end of the study (up to a maximum of 31 days post dose).. Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Mild Renal Impairment | 0/5 (0%) | 0/5 (0%) | 1/5 (20%) |
| Moderate Renal Impairment | 0/5 (0%) | 0/5 (0%) | 2/5 (40%) |
| Severe Renal Impairment | 0/8 (0%) | 0/8 (0%) | 1/8 (12.5%) |
| Event | Mild Renal Impairment | Moderate Renal Impairment | Severe Renal Impairment |
|---|---|---|---|
| NauseaGastrointestinal disorders | 0/5 | 1/5 | 0/8 |
| VomitingGastrointestinal disorders | 0/5 | 1/5 | 0/8 |
| HeadacheNervous system disorders | 1/5 | 1/5 | 0/8 |
| COVID-19Infections and infestations | 0/5 | 0/5 | 1/8 |
Safety population included all participants assigned to study intervention and who took at least 1 dose of study intervention.
| Age, Continuous(Years) | Mild Renal Impairment | Moderate Renal Impairment | Severe Renal Impairment | Total |
|---|---|---|---|---|
| Median | 68.0 (54 to 83) | 63.0 (55 to 71) | 66.5 (52 to 75) | 66.0 (52 to 83) |
| Sex: Female, Male(Participants) | Mild Renal Impairment | Moderate Renal Impairment | Severe Renal Impairment | Total |
|---|---|---|---|---|
| Female | 3 | 2 | 2 | 7 |
| Male | 2 | 3 | 6 | 11 |
| Race/Ethnicity, Customized(Participants) | Mild Renal Impairment | Moderate Renal Impairment | Severe Renal Impairment | Total |
|---|---|---|---|---|
| Black or African American | 1 | 3 | 1 | 5 |
| White | 4 | 2 | 7 | 13 |
| Body Mass Index (BMI)(kg/m^2) | Mild Renal Impairment | Moderate Renal Impairment | Severe Renal Impairment | Total |
|---|---|---|---|---|
| Mean | 29.1 ± 8.12 | 31.2 ± 6.89 | 33.7 ± 7.86 | 31.7 ± 7.49 |
| Body Surface Area (BSA)-Unnormalized Estimated Glomerular Filtration Rate (eGFR)(Milliliters per minute (mL/min)) | Mild Renal Impairment | Moderate Renal Impairment | Severe Renal Impairment | Total |
|---|---|---|---|---|
| Mean | 80.6 ± 8.26 | 48.7 ± 6.43 | 15.7 ± 8.31 | NA ± NA |
Documents are hosted by the registry — open the source record to download them.
Plan to share: No — Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.
Ran from Aug 2022 to primary completion in Jul 2023, 10 months.
Results were first posted in Nov 2024, 1 year 3 months after primary completion.
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Studies of the drug tested here: Lotiglipron