This is 2-part study. The primary objective of Part 1 is to evaluate safety and tolerability of single subcutaneous (SC) doses of PATAS in healthy subjects. The secondary objective of this study is to determine the pharmacokinetics (PK) of single SC doses of PATAS in healthy subjects. The primary objectives of Part 2 are to evaluate the safety and tolerability of 4 weekly SC doses of PATAS in subjects with T2D; and to determine the PK and pharmacodynamics (PD) of 4 weekly SC doses of PATAS in subjects with T2D. Secondary objectives of Part 2 include evaluation of the potential effect of multiple SC doses of PATAS on markers of glycemic control, as measured by glucose levels, insulin levels, and other metabolomic biomarkers and characterization of of adverse event (AE) profiles of the various dose levels of PATAS.
Excipient only formulation, without active compound
Eligibility
Sex: ALLMin age: 18 YearsMax age: 65 Years
Medical Language ↔ Plain English
Inclusion Criteria:
* Part 1: Single Ascending Dose Inclusion criteria
1. Healthy male and female subjects, 18 to 55 years of age, inclusive, at the time of signing the Informed Consent Form (ICF);
2. Willing and able to give written informed consent for participation in the study prior to the initiation of any Screening or study-specific procedures;
3. Body mass index (BMI) within the range of 20.0 to 35.0 kg/m2, inclusive, at Screening;
4. In generally good health, as judged by the Investigator, based upon medical/surgical history and the results of physical examination, vital signs, clinical laboratory assessments, and 12-lead electrocardiogram (ECG) at Screening and at Check-In (Day -1);
5. Female subjects must have a negative serum pregnancy test result at the Screening Visit and a negative urine pregnancy test at Check-In (Day -1) (prior to the first dose of study drug) and must not be pregnant, lactating, or planning a pregnancy from the Screening Visit to 90 days after the last dose of study drug;
6. Negative test result for severe acute respiratory syndrome coronavirus 2 at Check-In (Day -1); and
7. Willing to comply with all study procedures and requirements throughout the duration of the study.
Exclusion Criteria:
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1. Clinically significant history of asthma, eczema, or any other allergic condition or previous severe hypersensitivity; Note: Non-active hay fever is not exclusionary.
2. Liver function tests (alanine aminotransferase \[ALT\], aspartate aminotransferase \[AST\], alkaline phosphatase \[ALP\], total bilirubin) outside the following upper limits of normal (ULNs) at Screening or at Check-In (Day -1): a. For ALT and AST, measurements \> ULN; b. For ALP, measurements \>ULN; or c. For total bilirubin, measurements \> ULN.
3. Estimated glomerular filtration rate \</= 90 mL/min/1.73 m2 based on the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation at Screening or at Check-In (Day -1);
4. Thyroid-stimulating hormone (TSH) outside of reference range (e.g., TSH \<1 × lower limit of normal \[LLN\] or TSH \>1 × ULN) at Screening; Note: Abnormal TSH results will reflex to a free thyroxine (T4) test.
5. History of unexplained syncope, cardiac arrest, unexplained cardiac arrythmias or torsades de pointes, or structural heart disease;
6. Personal or family history of long QT syndrome;
7. Clinically significant history of any disease or disorder (i.e., gastrointestinal, cardiovascular, respiratory, renal, hepatic, neurological, dermatological, psychiatric, or metabolic) deemed to be exclusionary, as judged by the Investigator;
8. Abnormal pulse rate or blood pressure (BP) measurements at Screening, defined as: a. Pulse rate \<40 bpm or \>100 bpm; b. Systolic BP \< 90 mmHg or \>140 mmHg; or c. Diastolic BP \< 50 mmHg or \> 90 mmHg.
9. Clinically significant ECG abnormalities at Screening or at Check-In (Day -1), defined as prolongation of the average QTcF interval \> 450 ms for males and \>470 ms for females, or other clinically significant ECG abnormalities per Investigator discretion;
10. Positive for hepatitis B surface antigen, HIV antibody, or hepatitis C virus antibody at Screening;
11. Receipt of any investigational product within 30 days prior to first study drug administration (90 days for investigational biologic agents) or 5 half-lives prior to first study drug administration, whichever is greater, or participation in \>3 clinical studies within 12 months; 22. Known or suspected hypersensitivity to PATAS or any components of the formulation used (sodium hydroxide or mannitol);
Part 2: Multiple Ascending Dose Inclusion Criteria
1. Male and female subjects, 18 to 65 years of age, inclusive, at the time of signing the ICF;
2. Willing and able to give written informed consent for participation in the study prior to the initiation of any Screening or study-specific procedures;
3. A diagnosis of T2D \>6 months before Screening
4. Subjects should be on a stable dose of
1. an oral monotherapy (permitted monotherapies include metformin and dipeptidyl peptidase 4 inhibitors) for at least 90 days before Screening
2. or a dual therapy (including metformin and dipeptidyl peptidase 4 inhibitors) for at least 6 months before Screening
3. or managing the condition through diet and exercise for at least 90 days before Screening;
5. Glycated hemoglobin 7 % and \<10.5% at Screening;
6. BMI within the range of 25.0 to 40.0 kg/m2, inclusive, at Screening;
7. In generally good health, as judged by the Investigator, based upon medical/surgical history and the results of physical examination, vital signs, clinical laboratory assessments, and 12-lead ECG at Screening and at the pre-dose Check-In (Day -1);
8. Female subjects must have a negative serum pregnancy test result at the Screening Visit and a negative urine pregnancy test at the pre-dose Check-In (Day -1) (priorto the first dose of study drug) and must not be pregnant, lactating, or planning a pregnancy from the Screening Visit to 90 days after the last dose of study drug;
9. Female subjects of childbearing potential (i.e., ovulating, premenopausal, and not permanently surgically sterile) with male partners and all male subjects with female partners of childbearing potential will be included if they are either sexually inactive (complete abstinence from heterosexual activity if in line with the subject's preferred and usual lifestyle) and agree to continue complete abstinence for 90 days after the last administration of study drug, or, if sexually active, agree to use an effective contraceptive regimen during their participation in the study and for 90 days after the last administration of study drug. Effective contraceptive methods are defined as those with 90% or greater efficacy and include the following:
* For male subjects enrolled in the study: Condoms with spermicide; or Surgical sterilization (vasectomy) of the subject at least 6 months before Screening.
* For female subjects enrolled in the study: Intrauterine device for at least 90 days before Screening; Hormonal contraception (combination oral contraceptives, progestin-only oral contraceptives that inhibit ovulation, hormonal implants, progestin only injections, rings, or patches) for at least 90 days before Screening; or Bilateral tubal ligation for at least 90 days before Screening.
Note: Sexual abstinence is considered an effective method only if defined as refraining from heterosexual intercourse during the entire period of risk associated with the study treatments. Abstinence is only acceptable if in line with the subject's preferred and usual lifestyle. Periodic abstinence (calendar, symptothermal, post-ovulation methods), withdrawal (coitus interruptus), spermicides only, and lactational amenorrhea methods are not acceptable methods of contraception.
10. Female subjects of nonchildbearing potential will be included if they meet the following definition of nonchildbearing potential: are either surgically sterile (hysterectomy, bilateral salpingectomy, or bilateral oophorectomy at least 90 days before the Screening Visit) or postmenopausal, defined as spontaneous amenorrhea for at least 1 year, with FSH in the postmenopausal range at Screening, based on the central laboratory's ranges; and
11. Willing to comply with all study procedures and requirements throughout the duration of the study.
Part 2 Multiple Ascending Dose Inclusion Criteria 1. Poorly controlled diabetes which will interfere with participation in the trial in the opinion of the Investigator, e.g., brittle diabetes, extreme fluctuation of glucoses; 2. History of diabetic ketoacidosis or hyperosmolar coma in the 6 months prior to Screening; 3. History of level 3 hypoglycemia in the 6 months prior to Screening or a history of hypoglycemia unawareness; 4. History or current evidence of type 1 diabetes or any other form of diabetes (e.g., latent autoimmune diabetes in adults, maturity onset diabetes of the young, or secondary diabetes); 5. History of active or uncontrolled diabetic complications (i.e., neuropathy, retinopathy, nephropathy, gastroparesis); Note: Diabetic complications that are, in the opinion of the Investigator, stable in condition are permitted. 6. Clinically significant history of asthma, eczema, or any other allergic condition or previous severe hypersensitivity; Note: Non-active hay fever is not exclusionary. 7. Has an active or untreated malignancy or has been in remission from malignancy for 5 years except well-treated basal cell skin cancer or cervical cancer in situ; 8. Liver function tests (ALT, AST, ALP, total bilirubin) outside the following ULNs at Screening or at Check-In (Day -1):
1. For ALT and AST, measurements 3× ULN;
2. For ALP, measurements \>2 × ULN; or
3. For total bilirubin, measurements \>1.5 × ULN. 9. TSH \<1 × LLN or TSH \>1.5 × ULN at Screening; if a subject is on levothyroxine therapy, the subject should be on a stable dose for at least 6 weeks prior to Screening. 10. Estimated glomerular filtration rate 60 mL/min/1.73 m2 based on the CKD-EPI equation at Screening or at the pre-dose Check-In (Day -1); 11. History of unexplained syncope, cardiac arrest, unexplained cardiac arrythmias or torsades de pointes, or structural heart disease; 12. Personal or family history of long QT syndrome; 13. Clinically significant history of any disease or disorder (i.e., gastrointestinal, cardiovascular, respiratory, renal, hepatic, dermatological, or psychiatric) deemed to be exclusionary, as judged by the Investigator; 14. Recurrent or chronic pancreatitis 15. Abnormal pulse rate or BP measurements at Screening, defined as:
a. Pulse rate \<40 bpm or \>100 bpm; b. Systolic BP \<90 mmHg or \>160 mmHg; or c. Diastolic BP \<50 mmHg or \>100 mmHg. 16. Clinically significant ECG abnormalities at Screening or at Check-In (Day -1), defined as prolongation of the average QTcF interval \>450 ms for males and \>470 ms for females, or other clinically significant ECG abnormalities per Investigator discretion; 17. Any other clinically significant laboratory abnormality deemed to be exclusionary, as judged by the Investigator; 18. Use of insulin, sulfonylureas, peroxisome proliferator activated receptor gamma agonists, pramlintide, sodium-glucose cotransporter 2 (SGLT2) inhibitors glucagon-like peptide-1 receptor agonists within 90 days prior to Screening; 19. Initiation of any newly prescribed or over-the-counter drugs (including vitamins, hormone replacement therapy, supplements, and natural and herbal remedies \[e.g., St. John's wort\]) within 90 days prior to Screening and throughout the duration of the study; Note: Paracetamol (up to 3 g per day) and contraceptives are permitted. Subjects taking prescription medications and over-the-counter medications for the treatment of concurrent medical conditions (i.e., antihypertensive agents, aspirin, lipid-lowering agents) are permitted if subjects have been on a stable dose for 30 days prior to Screening.
20\. Use of systemic steroids for 7 days or any immunosuppressants in the 90 days prior to the pre-dose Check-In (Day -1); however, use of topical, ocular or inhaled steroids is permitted; 21. Positive urine drug screen (drugs of abuse) or urine cotinine test at Screening and/or the pre-dose Check-In (Day -1) or a history of drug/chemical abuse within 1 year prior to Screening; 22. Use of tobacco- or nicotine-containing products within 90 days prior to Screening or an unwillingness to abstain from the use of tobacco- or nicotine-containing products during the study; 23. Have typical weekly alcohol consumption of 14 alcoholic drinks. One drink is defined as 1 glass (approximately 10 to 12 oz) or 1 can (12 oz) of beer, 1 glass (approximately 4 to 5 oz) of wine, or 1 glass of distilled spirits (hard liquor) containing 1 oz of liquor; 24. Unwilling or unable to refrain from participating in contact sports or unaccustomed strenuous exercise for at least 72 hours prior to Screening, 72 hours prior to the first admission to the clinical site (e.g., the pre-dose Check-In \[Day - 1\]), and 72 hours prior to the visits to the clinical site on Day 8, Day 15, and Day 22 and the Follow-Up Visits on Day 28 and Day 35; 25. Unwilling to refrain from consuming liquids or foods containing caffeine or other xanthines from 48 hours prior to each admission to the clinical site (e.g., the predose Check-In \[Day -1\], Day 8, Day 15, and Day 22). Subjects should also refrain from consuming liquids or foods containing caffeine or other xanthines for 48 hours prior to the Follow-Up Visits on Day 28 and Day 35; 26. Subjects with extensive abdominal scarring, lipodystrophy, abdominal tattoos, or other such issues with the abdomen that would restrict the ability to perform multiple injections to the abdomen, per Investigator discretion; Note: Subjects are discouraged from getting abdominal tattoos during the study. 27. Lost or donated 450 mL of blood or blood products within 90 days prior to Screening, received a transfusion within 90 days prior to Screening, or plan to donate during the course of the study; 28. Positive for hepatitis B surface antigen, HIV antibody, or hepatitis C virus antibody at Screening; 29. Receipt of any investigational product within 30 days prior to first study drug administration (90 days for investigational biologic agents) or 5 half-lives, whichever is greater, or participation in \>3 clinical studies within 12 months; 30. Known or suspected hypersensitivity to PATAS or any components of the formulation used (sodium hydroxide or mannitol); or 31. Employee of the Sponsor, the CRO, or the clinical site (e.g., permanent employee, temporary contract worker, or designee responsible for the conduct of the study) or family members (e.g., spouse, parent, sibling, or child) of the Sponsor, CRO, or other clinical site employee
Locations (3)
Arizona Clinical Trials
Chandler, Arizona, United States
Clinical Pharmacology of Miami
Miami, Florida, United States
Progressive Medical Research
Port Orange, Florida, United States
Outcomes
Primary Outcomes
Phase 1B: Safety
Incidence and severity (using CTCAE version 5.0.) of treatment-emergent AEs and SAEs
Time frame: 29 days
OGTT
Oral glucose tolerance test
Time frame: Baseline, Day 28
Cmax
Maximum observed plasma concentration
Time frame: Pre-dose, Day 1, Day 2, Day 8, Day 15, Day 22, Day 23
Tmax
Time to Cmax
Time frame: Pre-dose, Day 1, Day 2, Day 8, Day 15, Day 22, Day 23
AUClast
Area under the concentration-time curve (AUC) from time 0 to the last measurable plasma concentration
Time frame: Pre-dose, Day 1, Day 2, Day 8, Day 15, Day 22, Day 23
AUCinf
AUC extrapolated to infinity (AUCinf);
Time frame: Pre-dose, Day 1, Day 2, Day 8, Day 15, Day 22, Day 23
T1/2
Apparent plasma terminal elimination half-life
Time frame: Pre-dose, Day 1, Day 2, Day 8, Day 15, Day 22, Day 23
CL/F
Apparent total plasma clearance after SC injection
Time frame: Pre-dose, Day 1, Day 2, Day 8, Day 15, Day 22, Day 23
HOMA-IR
Homeostatic Model Assessment of Insulin Resistance
Time frame: Baseline, Day 28
TyG
Changes in triglyceride-glucose index
Time frame: Baseline, Day 28
Adipo-IR
Changes in Adipose Tissue Insulin Resistance Index