Clinical trial NCT01963260: Single Rising Dose Study of MK-8723 in Healthy Participants and Participants With Immune Thrombocytopenia Purpura (MK-8723-001)
Official title: A Two-Part, Single Rising Dose Study to Assess the Safety, Pharmacokinetics and Pharmacodynamics of MK-8723 in Healthy Adults and Patients With Immune Thrombocytopenia Purpura
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Immune Thrombocytopenia Purpura
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2013-10-16
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The primary objectives of this study are to assess the safety and tolerability of single rising doses of MK-8723 in healthy adult participants and adult participants with chronic immune thrombocytopenia purpura (ITP) and to assess pharmacodynamics of MK-8723 in participants with ITP. The primary hypothesis is that the true placebo-adjusted platelet response rate to MK-8723 in adult patients with chronic ITP is \>50%.

Detailed description: In Part 1 of the trial, safety and pharmacokinetics of MK-8723 will be evaluated in healthy participants. In Part 2 of the trial, safety, pharmacokinetics, and pharmacodynamics will be evaluated among participants with ITP. In Part 1, dose escalation will occur in up to 5 serial panels of participants; each participant will receive a single intravenous (IV) dose of MK-8723 (or placebo). In Part 2, dose escalation will occur in up to 3 serial panels of participants with ITP; each participant will receive a single IV dose of MK-8723 (or placebo), once safety and tolerability of the corresponding dose is shown in Part 1. Amendment 3 specified a re-enrollment procedure for eligible participants in Part 2 to participate in more than one dosing panel.

Eligibility criteria: Inclusion Criteria (Part 1):

* Female participants must be non-pregnant, non-breast feeding, and of non-childbearing potential
* Has a Body Mass Index (BMI) \<=32 kg/m\^2
* Has a body weight \>= 50 kg and \<= 100 kg
* Has been judged to be in good health based on medical history, physical examination, vital sign measurements, electrocardiogram (ECG), and laboratory safety tests
* Non-smoker or has not used nicotine or nicotine-containing products for at least 3 months

Inclusion Criteria (Part 2):

* Has been diagnosed with ITP at least 3 months prior
* Female ITP participants must be non-pregnant, non-breast feeding, and either of 1) non-childbearing potential or 2) must have serum beta human chorionic gonadotropin (HCG) level consistent with a non-pregnant state, and agree to use acceptable contraception from pretrial period until 84 days postdose
* Has a BMI \<=36 kg/m\^2
* Has been judged to be in good health, other than ITP diagnosis, based on medical history, physical examination, vital sign measurements, ECG, and laboratory safety tests

Exclusion Criteria (Part 1):

* Has a history or clinically significant endocrine, gastrointestinal, cardiovascular, hematological, hepatic, immunological, renal, respiratory, genitourinary, or major neurological abnormalities or diseases
* Has a history of cancer (malignancy)
* Has a history of significant multiple and/or severe allergies or has had an anaphylactic reaction or significant intolerability to prescription or non-prescription drugs or food
* Is positive for hepatitis B surface antigen, hepatitis C antibodies, or human immunodeficiency virus (HIV)
* Has had major surgery or donated or lost 1 unit of blood in the 4 weeks prior
* Has participated in another investigational trial within 4 weeks (12 weeks for biologics)
* Has received a live virus vaccination within 42 days or plans to receive such while participating in the trial
* Is unable to refrain from or anticipates the use of any medication, including prescription and non-prescription drugs and herbal remedies from 2 weeks prior and for the duration of the trial
* Consumes greater than 3 glasses of alcoholic beverages per day
* Consumes greater than 6 servings of caffeine-containing beverages per day
* Is currently a regular user of any illicit drugs or has a history of drug and/or alcohol abuse within 3 months
* Has a history of ITP or other autoimmune disease
* Has an active infection that is clinically significant

Exclusion Criteria (Part 2):

* Has a comorbid and significant hematological or immunological disorder
* Has a history of significant multiple and/or severe allergies or has had an anaphylactic reaction or significant intolerability to prescription or non-prescription drugs or food
* Is positive for hepatitis B surface antigen, hepatitis C antibodies, or HIV
* Has had major surgery or donated or lost 1 unit of blood within 4 weeks
* Has participated in another investigational trial within 4 weeks (12 weeks for biologics), excluding prior participation in the current study
* Has a history of ITP unresponsive to intravenous immunoglobulin (IVIG)
* Has had systemic corticosteroid use within 1 month (with the exception of stable low dose oral corticosteroids)
* Has had systemic IVIG or other systemic immunomodulatory therapy, excluding MK-8723 administration in the current study, within 3 months
* Has received a thrombopoietin receptor antagonist within 3 months
* Is unable to refrain from using thrombopoietin receptor agonists and/or systemic immune modulatory medications throughout the study
* Has received a live virus vaccine within 42 days prior or plans to receive such during the trial
* Consumes greater than 3 alcoholic beverages per day
* Consumes greater than 6 servings of caffeine-containing beverages per day
* Is currently a regular user of any illicit drugs or has a history of drug and/or alcohol abuse within 3 months
* Has clinical evidence of bleeding or coagulopathy including petechial rash, easy bruising, or excessive gingival bleeding with routine dental hygiene
* Has an active infection that is clinically significant

Primary outcomes:
measure: Number of Participants Experiencing an Adverse Event
timeFrame: Up to 84 days
measure: Number of Participants Discontinuing Study Due to an Adverse Event (AE)
timeFrame: Up to 84 Days
measure: Number of Participants With a Positive Platelet Response to MK-8723
timeFrame: Up to Day 14
Secondary outcomes:
measure: Area Under the Concentration-time Curve of MK-8723 From Time 0 to Infinity (AUC0-∞) Among Healthy Participants and Participants With ITP
timeFrame: All dose groups: Predose and 4 (end of infusion), 6, 12, 24 hrs postdose and Days 3, 4, 5, 7, 10, 14, 21, 28; 30 mg/kg and 100 mg/kg dose groups: Days 43, 56, 71, 84
measure: Maximum Concentration (Cmax) of MK-8723 Among Healthy Participants and Participants With ITP
timeFrame: All dose groups: Predose and 4 (end of infusion), 6, 12, 24 hrs postdose and Days 3, 4, 5, 7, 10, 14, 21, 28; 30 mg/kg and 100 mg/kg dose groups: Days 43, 56, 71, 84
Other outcomes:
Locations:
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References: