A Randomized SAD and MAD Study Evaluating the Safety and Tolerability of RPh201 in Healthy Subjects and in Adults With Alzheimer's Disease

This study is currently recruiting participants. (see Contacts and Locations)
Verified December 2012 by Regenera Pharma Ltd
Sponsor:
Collaborator:
Kendle Toronto, Inc, a wholly-owned subsidiary of INC Research LLC
Information provided by (Responsible Party):
Regenera Pharma Ltd
ClinicalTrials.gov Identifier:
NCT01513967
First received: January 17, 2012
Last updated: December 6, 2012
Last verified: December 2012
  Purpose

This is a dual-centre, Phase I/IIa study, in healthy subjects and subjects with AD to investigate the safety, tolerability, cognitive, and behavioural effects of RPh201. The study will be divided into three parts: A, B, and C


Condition Intervention Phase
Moderate to Severe Alzheimer
Alzheimer Disease
Drug: RPh201, botanical drug product
Drug: Placebo
Drug: RPh201, botanical extract product
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Official Title: A Randomized Single and Multiple Dose Study Evaluating the Safety and Tolerability of RPh201 in Healthy Subjects and in Adults With Alzheimer's Disease

Resource links provided by NLM:


Further study details as provided by Regenera Pharma Ltd:

Primary Outcome Measures:
  • The primary objective: to evaluate the safety and tolerability of RPh201 after single and multiple rising doses. [ Time Frame: up to 6 month ] [ Designated as safety issue: Yes ]
    Safety and tolerability following single and multiple ascending oral doses as assessed by adverse events, vital signs, neurological examination, 12-lead ECG, Columbia-Suicide Severity Rating Scale (C-SSRS), clinical laboratory and physical exam.


Secondary Outcome Measures:
  • To evaluate efficacy of RPh201 in subjects with AD [ Time Frame: up to 6 month ] [ Designated as safety issue: No ]
    • The cognitive and behavioural effects of multiple SC doses of RPh201 in subjects with AD will be assessed using the MMSE, SIB, CDT, and WLG, and caregiver burden will be evaluated using the Caregiver Burden Scale.
    • The electrophysiological responses to RPh201 in subjects with AD will be measured by Brain Network Activation (BNA) consisting of oddball and Sternberg paradigms.


Estimated Enrollment: 56
Study Start Date: January 2012
Estimated Study Completion Date: February 2014
Estimated Primary Completion Date: December 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Part A, SAD Treatment 1
RPh201 single dose (SAD Low Dose )
Drug: RPh201, botanical drug product
SC administration at varying doses
Placebo Comparator: Part A, SAD Placebo 1
Placebo single dose (SAD Low Dose )
Drug: Placebo
SC administration at varying doses
Experimental: Part A, SAD Treatment 2
RPh201 single dose (SAD Mid Dose )
Drug: RPh201, botanical drug product
SC administration at varying doses
Placebo Comparator: Part A, SAD Placebo 2
Placebo single dose (SAD Mid Dose )
Drug: Placebo
SC administration at varying doses
Experimental: Part A, SAD Treatment 3
RPh201 single dose (SAD High Dose )
Drug: RPh201, botanical drug product
SC administration at varying doses
Placebo Comparator: Part A, SAD Placebo 3
Placebo single dose (SAD High Dose )
Drug: Placebo
SC administration at varying doses
Experimental: Part B, MAD Treatment 1
RPh201 multiple dose (MAD Low Dose )
Drug: RPh201, botanical drug product
SC administration at varying doses
Placebo Comparator: Part B, MAD Placebo 1
Placebo multiple dose (MAD Low Dose )
Drug: Placebo
SC administration at varying doses
Experimental: Part B, MAD Treatment 2
RPh201 multiple dose (MAD Mid Dose )
Drug: RPh201, botanical drug product
SC administration at varying doses
Placebo Comparator: Part B, MAD Placebo 2
Placebo multiple dose (MAD Mid Dose )
Drug: Placebo
SC administration at varying doses
Experimental: Part B, MAD Treatment 3
RPh201 multiple dose (MAD High Dose )
Drug: RPh201, botanical drug product
SC administration at varying doses
Placebo Comparator: Part B, MAD Placebo 3
Placebo multiple dose (MAD High Dose )
Drug: Placebo
SC administration at varying doses
Experimental: Part C, AD patient, Treatment
3 month treatment schedule, consisting of bi-weekly administration of the RPh201
Drug: RPh201, botanical extract product
3-month treatment schedule, consisting of bi-weekly SC administration of the study drug followed by a follow up period 3 months post end of the last treatment day
Experimental: Part C, AD patients Placebo
3-month treatment schedule, consisting of bi-weekly administration of the placebo
Drug: Placebo
3-month treatment schedule, consisting of bi-weekly SC administration of the placebo followed by a follow up period 3 months post end of the last treatment day

Detailed Description:

The primary objective of this study is to evaluate the safety and tolerability of RPh201 after single and multiple rising doses. This study is designed with sufficient time in between dose escalations to allow for an interim analysis of safety and tolerability data as this is considered the safest approach to assess the effects of a compound with an undefined mechanism and therapeutic target.

This protocol is written with some flexibility to accommodate the inherent dynamic nature of Phase I clinical studies. Modifications to the dose, dosing regimen, and/or clinical or laboratory procedures currently outlined below may be required to achieve the scientific goals of the study objectives and/or to ensure appropriate safety monitoring of the study subjects. Interim safety analyses will guide dose escalation/reduction in the trial.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

For PART A AND PART B (healthy volunteers, SAD and MAD)

Inclusion Criteria:

  • healthy male or female subjects 18 to 65 years of age, inclusive
  • body mass index (BMI) within the range of 18.0 to 33.0 kg/m2, inclusive, and a minimum weight of at least 50.0 kg at Screening
  • female subjects of childbearing potential must be practicing abstinence or using and willing to continue using two medically acceptable form of birth control for at least 1 month prior to Screening (at least 3 months for oral and transdermal contraceptives) and for at least 1 month after the last study drug administration. Medically acceptable forms of contraception include oral or patch hormonal contraceptives, intrauterine device, progestin implant or injection, bilateral tubal ligation, or double-barrier (i.e., male condom in addition to a diaphragm or a contraceptive sponge).
  • female subjects of non-childbearing potential must be amenorrheic for at least 2 years or had a hysterectomy and/or bilateral oophorectomy/salpingo-oophorectomy (as determined by subject medical history)
  • male subjects of reproductive potential with a partner(s) of childbearing potential, must be using and willing to continue to using two medically acceptable contraceptive precautions from Screening and for at least 1 month after the last study drug administration. Medically acceptable forms of contraception include abstinence, vasectomy, or male condom for subjects
  • female subjects must have a negative pregnancy test
  • able to speak, read, and understand English sufficiently to understand the nature of the study, to provide written informed consent, and to allow completion of all study assessments
  • must understand and provide written informed consent prior to the initiation of any protocol-specific procedures
  • must be willing and able to abide by all study requirements and restrictions

Exclusion Criteria:

  • current drug or alcohol dependence (excluding caffeine), based on self-report, including subjects who have been in a drug rehabilitation program
  • current smoker or a history of using tobacco products within 3 months prior to Screening
  • clinically significant abnormalities on physical examination, medical history, 12-lead ECG (i.e., QTc > 440 for male subjects and > 450 for female subjects), vital signs, or laboratory values, as judged by the investigator or designee
  • history or presence of any clinically significant illness (e.g., cardiovascular, pulmonary, hepatic, renal, hematologic, gastrointestinal, endocrine, immunologic, dermatologic, neurologic, oncologic, musculoskeletal, or psychiatric) or any other condition, which in the opinion of the investigator would jeopardize the safety of the subject or the validity of the study results
  • use of a non-prescription drug within 7 days prior to the first drug administration. Subjects who have taken over-the-counter medication may still be entered into the study, if in the opinion of the investigator or designee, the medication received will not interfere with the study procedures or data integrity or compromise the safety of the subject
  • use of any prescription medications, recreational drugs, or natural health products (except vitamin or mineral supplements, acceptable forms of birth control, and hormone replacement) within 14 days prior to first drug administration or throughout the study, unless in the opinion of the investigator or designee, the product will not interfere with the study procedures or data integrity or compromise the safety of the subject
  • positive urine drug screen
  • positive breath alcohol test. If a subject presents with positive breath alcohol test, the subject may be rescheduled at the discretion of the investigator or designee
  • female subjects who are currently pregnant or lactating or who are planning to become pregnant within 60 days of last study drug administration
  • history of allergy or hypersensitivity to mastic or related drugs (e.g., mastic gum, mastic resin, Chios mastic powder, retsina wine, Mastic Gum 500, Mastic Gum Elma 50, Nutricology Mastic Gum)
  • history of allergy or hypersensitivity to cottonseed oil
  • positive for Hepatitis B, Hepatitis C, or HIV
  • current or pending legal charges or currently on probation
  • treatment with any investigational drug within 30 days prior to first drug administration in the treatment phase
  • a subject who, in the opinion of the investigator or designee, is not considered to be suitable and is unlikely to comply with the study protocol for any reason

For PART C (subjects with Alzheimer's Disease)

Inclusion Criteria:

  • males and females ages ≥ 55 years of age at Screening visit
  • diagnosis of AD, consistent with criteria from both the National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association (NINCDS-ADRDA) Criteria for Probable AD and Diagnostic and Statistical Manual of Mental Disorders - IV TR (DSM-IV TR) Criteria for Dementia of the Alzheimer's Type
  • Mini-Mental Status Evaluation (MMSE) score of 5-15, inclusive, at Screening visit
  • Rosen-Modified Hachninski Ischemia score of ≤ 4 at Screening visit
  • subjects and caregivers must be able to read, write, and speak the language in which psychometric tests are provided with acceptable visual and auditory acuity
  • subject must have a reliable informant (caregiver) to provide collateral history and who will facilitate the subject's full participation in the study
  • subject and caregivers must provide written informed consent and be willing to comply with scheduled visits, treatment plan, laboratory tests, and other trial procedures
  • subjects may continue on background cholinesterase inhibitor and/or memantine
  • subjects must be in satisfactory good health, in the opinion of the investigator, based on medical history, physical examination, vital signs, 12-lead ECG, and laboratory tests
  • magnetic resonance imaging (MRI) or computed tomography (CT) within 12 months of Screening visit consistent with a diagnosis of Probable AD without any other clinically significant findings

Exclusion Criteria:

  • diagnosis or history of other dementia or neurodegenerative disorders causing cognitive impairment (e.g., Parkinson's disease, Lewy body disease, Fronto-temporal Dementia, alcohol and drug abuse, Traumatic Brain Injury).
  • subjects receiving immunosuppressants, tricyclic anti-depressants, anticoagulants, or chemotherapeutic agents
  • hypertension not adequately controlled, per investigator's judgment
  • poorly controlled Type 1 and/or Type 2 diabetes, per investigator's judgment
  • women of child bearing potential who are not using an effective method of birth control
  • any other medical condition or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or that may interfere with the interpretation of study results, and that, in the judgment of the investigator, would make the subject inappropriate for entry into this study.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01513967

Contacts
Contact: Konstantin Adamsky, Ph.D. +972-8-9316306 kostia@regenerapharma.com

Locations
Canada, Ontario
Kendle Early Stage - Toronto Recruiting
Toronto, Ontario, Canada, M5V 2T3
Principal Investigator: Janice Faulknor, MD         
Toronto Memory Program Not yet recruiting
Toronto, Ontario, Canada, M3B 2S7
Principal Investigator: Sharon Cohen, MD         
Sponsors and Collaborators
Regenera Pharma Ltd
Kendle Toronto, Inc, a wholly-owned subsidiary of INC Research LLC
Investigators
Principal Investigator: Janice Faulknor, MD Kendle Early Stage - Toronto
Principal Investigator: Sharon Cohen, MD Toronto Memory Program
  More Information

No publications provided

Responsible Party: Regenera Pharma Ltd
ClinicalTrials.gov Identifier: NCT01513967     History of Changes
Other Study ID Numbers: RGN-ADC-001
Study First Received: January 17, 2012
Last Updated: December 6, 2012
Health Authority: Canada: Health Canada

Keywords provided by Regenera Pharma Ltd:
Alzheimer,
dementia

Additional relevant MeSH terms:
Alzheimer Disease
Dementia
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Tauopathies
Neurodegenerative Diseases
Delirium, Dementia, Amnestic, Cognitive Disorders
Mental Disorders

ClinicalTrials.gov processed this record on September 22, 2014