The Effects of BAY1193397 on Skin Capillary Blood Flow and Transcutaneous Oxygen Pressure

NCT03128320 | Completed Phase 2

• 2 other identifiers: 175002015-003799-63
• Study Type: interventional
• Target: 23
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of the study is to analyse skin blood flow in diabetic patients. The patients receive a single dose of placebo, 1 mg BAY1193397, and 5 mg BAY1193397. The analysis of safety and tolerability are secondary objectives of this study.

Conditions

Diabetic Foot

Outcome Measures

Primary Outcomes (4)

• Change in resting capillary blood flow velocity (CBV)

  = resting CBV after study drug administration - resting CBV before study drug administration

  Before and after treatment with study drug (within 1-3 hours after treatment with study drug)

• Change in peak CBV during reactive hyperemia

  = peak CBV after study drug administration - peak CBV before study drug administration

  Before and after treatment with study drug (within 1-3 hours after treatment with study drug)

• Change in time to peak CBV during reactive hyperemia

  = time to peak CBV after study drug administration - time to peak CBV before study drug administration

  Before and after treatment with study drug (within 1-3 hours after treatment with study drug)

• Change in transcutaneous oxygen pressure (TcPO2)

  = TcPO2 after study drug administration - TcPO2 before study drug administration

  Before and after treatment with study drug (within 1-3 hours after treatment with study drug)

Secondary Outcomes (2)

• Number of subjects with treatment-emergent adverse events (TEAEs)

  From first application of study medication up to 2 days after end of treatment with study medication

• Number of subjects with TEAEs in different severity

  From first application of study medication up to 2 days after end of treatment with study medication

Study Arms (3)

BAY1193397/Placebo (sequence A-B-C)

EXPERIMENTAL

Subjects with type II diabetes who follow treatment sequence A-B-C. Single oral dose of a placebo tablet in the first intervention period (Treatment A); followed by single oral dose of 1 mg BAY1193397 (Treatment B); then single oral dose of 5 mg BAY1193397 IR tablet under fasted state in the third intervention period (Treatment C). A wash-out phase of approximately 120 - 360 hours was maintained between each treatment.

Drug: BAY1193397; Drug: Placebo

BAY1193397/Placebo (sequence B-C-A)

EXPERIMENTAL

Subjects with type II diabetes who follow treatment sequence B-C-A. Single oral dose of 1 mg BAY1193397 in the first intervention period (Treatment B); followed by single oral dose of 5 mg BAY1193397 IR tablet under fasted state in the second intervention period (Treatment C), then single oral dose of a placebo tablet under fasted conditions in the third intervention period (Treatment A). A wash-out phase of approximately 120 - 360 hours was maintained between each treatment.

Drug: BAY1193397; Drug: Placebo

BAY1193397/Placebo (sequence B-A-C)

EXPERIMENTAL

Subjects with type II diabetes who follow treatment sequence B-A-C. Single oral dose of 1 mg BAY1193397 in the first intervention period (Treatment B); followed by single oral dose of a placebo tablet in the second intervention period (Treatment A), then 5 mg BAY1193397 IR tablet under fasted conditions in the third intervention period (Treatment C). A wash-out phase of approximately 120 - 360 hours was maintained between each treatment.

Drug: BAY1193397; Drug: Placebo

Interventions

BAY1193397 DRUG

Single dose of 1 mg BAY1193397 given in the fasted state

BAY1193397/Placebo (sequence A-B-C); BAY1193397/Placebo (sequence B-A-C); BAY1193397/Placebo (sequence B-C-A)

Placebo DRUG

Single dose of placebo given in the fasted state

BAY1193397/Placebo (sequence A-B-C); BAY1193397/Placebo (sequence B-A-C); BAY1193397/Placebo (sequence B-C-A)

Eligibility Criteria

• Age: 55 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• The informed consent must be signed before any study specific tests or procedures are done (patient must be able to give informed consent, no legal representative allowed)
• Patients with a diagnosis of type II diabetes mellitus and PAD (peripheral artery disease) and/or microangiopathy as evidenced by at least one of the following criteria:
• TBPI (toe / brachial blood pressure index) \< 0.7 at screening
• ischemic or neuro-ischemic DFU (diabetic food ulcer) in medical history (verified by medical records)
• clinical diagnosis of PAD in medical history (verified by medical records)
• diagnosis of nephropathy that is most likely due to diabetes mellitus type II
• diagnosis of diabetic retinopathy
• diagnosis of diabetic polyneuropathy
• Age 55 to 75 years (inclusive) at the screening visit
• Patients are expected to be on stable medication during study conduct. No planned changes in drug therapy during active treatment period of the study (i.e. from treatment period 1 to treatment period 3) is allowed.
• Men or confirmed postmenopausal women (defined as exhibiting spontaneous amenorrhea for at least 12 months before screening or as exhibiting spontaneous amenorrhea for 6 months before screening with documented serum follicle-stimulating hormone \[FSH\] levels \> 40 mIU/mL) or women without childbearing potential based on surgical treatment 6 weeks before screening such as bilateral tubal ligation, bilateral oophorectomy with or without hysterectomy (documented by medical report verification). Male patients, who are sexually active and have not been surgically sterilized must agree to use two reliable and acceptable methods of contraception simultaneously (one method used by the study patient and one method used by the partner) during the study and for 12 weeks after receiving the investigational medicinal product and not to act as sperm donor for 12 weeks after dosing. Acceptable methods of contraception include for example: a) condoms (male or female) with or without a spermicidal agent b) diaphragm or cervical cap with spermicide c) intrauterine device d) hormone-based contraception
• Ability to understand and follow study related instructions

You may not qualify if:

• Patients with existing lower limb ulcers
• Patients with nailfold capillaries at the great toe that are technically difficult to assess
• Patients suffering from PAD Fontaine Stage 4
• Patients requiring planned revascularization
• Patients suffering from diseases other than diabetes mellitus that are known to lead to disturbances in skin microcirculation or interfering with the method of measurement such as Raynaud's disease, collagen vascular disorders , atopic dermatitis, psoriasis
• Myocardial infarction, acute coronary syndrome, transient ischemic attack (TIA), stroke, revascularization, angioplasty within 3 months prior to randomization
• Any planned surgical intervention during the course of the study
• Medical condition or history thereof or any deviation from normal laboratory values that in the opinion of the investigator would impair the ability to complete the planned study procedures.
• Any surgical or medical condition which significantly alters absorption, distribution, metabolism or excretion of study drugs, including, but not limited to: history of major gastrointestinal (GI) tract surgery, inflammatory bowel disease, currently active gastritis, pancreatitis, treatment with cholestyramine and colestipol resins
• Patients with HbA1c \> 12% (\> 108 mmol/mol) at the screening visit
• Any other condition or therapy, which would make the subject unsuitable for this study and will not allow participation for the full planned study period (e.g. active malignancy or other condition limiting life expectancy to less than 12 months)
• Use of alpha- or beta-AR (adrenoreceptor) agonists
• Use of alpha-AR antagonists
• Use of serotonin/norepinephrine reuptake inhibitors (SNRIs)
• Use of tricyclic antidepressants at a dose equivalent of more than 50 mg amitryptyline

Sponsors & Collaborators

• Bayer: lead

Study Sites (1)

Royal Devon & Exeter Hospital

Exeter, Devon, EX2 5AX, United Kingdom

Location

Related Links

• Click here to find information about studies related to Bayer Healthcare products conducted in Europe.
• Click here to find results for studies related to Bayer Healthcare products.

MeSH Terms

Conditions

Diabetic Foot

Condition Hierarchy (Ancestors)

Diabetic Angiopathies; Vascular Diseases; Cardiovascular Diseases; Foot Ulcer; Leg Ulcer; Skin Ulcer; Skin Diseases; Skin and Connective Tissue Diseases; Diabetes Complications; Diabetes Mellitus; Endocrine System Diseases; Diabetic Neuropathies

Study Officials

• Bayer Study Director

  Bayer

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: OTHER
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 21, 2017
• First Posted: April 25, 2017
• Study Start: May 25, 2017
• Primary Completion: September 6, 2019
• Study Completion: October 28, 2019
• Last Updated: August 13, 2020

Record last verified: 2020-08

Locations

GB (1)