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Early Signs of Efficacy Study With Riociguat in Adult Homozygous Delta F508 Cystic Fibrosis Patients

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT02170025
Recruitment Status : Terminated (Based on multiple factors, the design of part 2 is no longer appropriate. There were no safety concerns identified)
First Posted : June 23, 2014
Last Update Posted : November 6, 2017
Sponsor:
Collaborator:
Information provided by (Responsible Party):

Study Description
Brief Summary:
Assessment of the safety, tolerability and early signs of efficacy of three times a day orally administered BAY63-2521 in adult delta F508 homozygous Cystic Fibrosis patients not on treatment with Orkambi

Condition or disease Intervention/treatment Phase
Cystic Fibrosis Drug: Riociguat (Adempas, BAY63-2521) Drug: Placebo Phase 2

Detailed Description:
The study consists of two parts. The first part is double-blind, randomized and placebo-controlled. The second part has an open-label study design. In part 1 patients on Orkambi or other CFTR-modulators are excluded. In part 2 patients on Orkambi are allowed to be included under certain conditions.

Study Design

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 21 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Multi-center Phase 2 Study to Assess the Safety, Tolerability and Early Signs of Efficacy of Tid Orally Administered BAY63-2521 in Adult Delta F508 Homozygous Cystic Fibrosis Patients
Actual Study Start Date : September 30, 2014
Primary Completion Date : January 17, 2017
Study Completion Date : August 31, 2017

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Cystic Fibrosis
Drug Information available for: Riociguat
U.S. FDA Resources

Arms and Interventions

Arm Intervention/treatment
Experimental: Arm 1: BAY63-2521
Part 1: two dose levels (0.5 and 1 mg) of BAY63-2521 in patients without Orkambi therapy
Drug: Riociguat (Adempas, BAY63-2521)
Pat 1: The patients will receive 0.5 mg three times a day for the initial 14 days and a 1 mg for the second 14 days.
Experimental: Arm 2: Placebo
Part 1: Placebo
Drug: Placebo
Part 1: Placebo tablet, three times a day for duration of 28 days
Experimental: Arm 3: BAY63-2521
Part 2: four dose levels (0.25, 0.5, 1 and 2 mg) of BAY63-2521 in patients without Orkambi therapy
Drug: Riociguat (Adempas, BAY63-2521)
Part 2: Patients not on Orkambi therapy will receive 0.25 mg BAY63-2521 tid for 14 days, increasing to 0.5 mg, 1 mg and 2 mg for 14 days each.
Experimental: Arm 4: BAY63-2521
Part 2: four dose levels (0.25, 0.5, 1 and 2 mg) of BAY63-2521 in patients with Orkambi therapy
Drug: Riociguat (Adempas, BAY63-2521)
Part 2: Patients receiving Orkambi therapy for at least 3 months as their standard of care will receive 0.25 mg BAY63-2521 tid for 14 days, increasing to 0.5 mg, 1 mg and 2 mg for 14 days each.


Outcome Measures

Primary Outcome Measures :
  1. Change of sweat chloride content from baseline [ Time Frame: Baseline, at day 14 and day 28 in study part 1 and baseline, day 14, 28, 42 and 56 in study part 2 ]

Eligibility Criteria

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Signed informed consent available before any study specific tests or procedures are performed
  • Patients must be at least 18 years of age at time of inclusion (i.e. upon signature of informed consent)
  • Patient diagnosed with Cystic Fibrosis according to standard criteria (i.e. either elevated sweat chloride content above 60 mmol/ L and/ or genetic testing)
  • Patient is homozygous for the deltaF508 mutation
  • Patient has a mild-to-moderate stage of lung disease as determined by FEV1 (FEV1 between 40 and 100% predicted)
  • Patient has a stable condition of lung disease (no ongoing or recent pulmonary exacerbation and no change in current treatment) within the last 4 weeks prior to screening
  • Ability and willingness to understand and follow study procedures for the entire study
  • Patients do not smoke. Patients with a history of smoking can be included, if they have refrained from smoking for the last 3 months. If a patients starts smoking during the study participation, he/ she needs to be excluded and considered to be a drop out
  • Body mass index (BMI): ≥ 16 kg/ m² (calculated by dividing the patient's weight by the square of his/ her height [kg/ m2])

Inclusion criterion valid for study part 1 only:

- Women of childbearing potential must agree to use adequate contraception when sexually active. 'Adequate contraception' is defined as one highly effective form of contraception (intrauterine devices [IUD], contraceptive implants or tubal sterilization) or a combination of methods (hormone method with a barrier method ). If a partner's vasectomy is the chosen method of contraception or if a partner has documented azoospermia, a hormone or barrier method must be used in combination. Adequate contraception is required from the signing of the informed consent form up until 4 weeks after the last study drug administration

Inclusion criteria valid for study part 2 only:

  • Women of childbearing potential must agree to use adequate contraception when sexually active. 'Adequate contraception' is defined as one highly effective form of contraception (intrauterine devices [IUD], contraceptive implants or tubal sterilization) or a combination of methods (hormone method with a barrier method). For patients on Orkambi hormonal methods (including hormonal oral contraceptives) cannot be accepted in this study. They need to choose non-hormonal methods. If a partner's vasectomy is the chosen method of contraception or if a partner has documented azoospermia, a hormone or barrier method must be used in combination. Adequate contraception is required from the signing of the informed consent form up until 4 weeks after the last study drug administration
  • Patients receiving Orkambi (Lumcaftor + Ivacaftor) as part of their standard care need to be on stable Orkambi treatment for at least 3 months prior to screening (patients on Lumacaftor and/or Ivacaftor are excluded in part 1)

Exclusion Criteria:

  • Patients with Cystic Fibrosis with any background other than homozygous deltaF508 mutation
  • Exclusion criterion only valid for study part 1: Patients receiving treatment with Lumacaftor and/ or Ivacaftor
  • Active state of hemoptysis or pulmonary hemorrhage, including those events managed by bronchial artery embolization. Also any history of moderate hemoptysis within the 3 months prior to inclusion
  • Any history of pneumothorax, bronchial artery embolization or massive hemoptysis. Massive hemoptysis being defined as acute bleeding >240 mL in a 24-hour period or recurrent bleeding >100 mL/ d over several days
  • A positive sputum culture for Burkholderia cenocepacia, Burkholderia dolosa, and/ or Mycobacterium absessus either currently or within the previous year
  • Active allergic broncho-pulmonary aspergillosis
  • Current pulmonary exacerbation
  • Known history of solid organ transplantation
  • Known history of any form of pulmonary hypertension
  • Clinically relevant deviations of the screened laboratory parameters from reference ranges outside of expected changes for Cystic Fibrosis patients, especially a hemoglobin value below 110 g/L or a creatinine clearance based on the Cockcroft-Gault formula < 15 ml/ min
Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02170025


  Show 23 Study Locations
Sponsors and Collaborators
Bayer
Merck Sharp & Dohme Corp.
Investigators
Study Director: Bayer Study Director Bayer
More Information

Additional Information:
Responsible Party: Bayer
ClinicalTrials.gov Identifier: NCT02170025     History of Changes
Other Study ID Numbers: 17020
2013-004595-35 ( EudraCT Number )
First Posted: June 23, 2014    Key Record Dates
Last Update Posted: November 6, 2017
Last Verified: October 2017

Keywords provided by Bayer:
Cystic fibrosis
delta F508
Safety
Tolerability
Sweat Chloride
Pharmacokinetics

Additional relevant MeSH terms:
Fibrosis
Cystic Fibrosis
Pathologic Processes
Pancreatic Diseases
Digestive System Diseases
Lung Diseases
Respiratory Tract Diseases
Genetic Diseases, Inborn
Infant, Newborn, Diseases
Prednisolone acetate
Methylprednisolone acetate
Methylprednisolone
Methylprednisolone Hemisuccinate
Prednisolone
Prednisolone hemisuccinate
Prednisolone phosphate
Anti-Inflammatory Agents
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Gastrointestinal Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Neuroprotective Agents
Protective Agents
Antineoplastic Agents, Hormonal
Antineoplastic Agents