ZIRCON: A Study to Evaluate Treatment of Hepatitis C Virus Infection in Pediatric Subjects

• Sponsor: AbbVie (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02486406
• Collaborator: (none)
• Enrollment: 64
• Locations: 21
• Arms: 4
• Actual Duration (Months): 60.7
• Patients Per Site: 3
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

This was a Phase 2/3, open-label, multicenter study to evaluate the pharmacokinetics (PK), efficacy, and safety of ombitasvir/paritaprevir/ritonavir (OBV/PTV/RTV) with or without dasabuvir (DSV) and with or without ribavirin (RBV) in Hepatitis C virus (HCV) genotype 1 or 4 (GT1 or GT4)-infected pediatric participants of ≥ 3 to 17 years of age.

Condition or Disease	Intervention/Treatment	Phase
Chronic Hepatitis C Infection	Drug: Ombitasvir/paritaprevir/ritonavir; Drug: Dasabuvir; Drug: Ribavirin; Drug: Ombitasvir mini tablet; Drug: Paritaprevir mini tablet; Drug: Ritonavir mini tablet; Drug: Dasabuvir mini tablet; Drug: Ribavirin solution	Phase 2/Phase 3

Detailed Description

The study population for Part 1, the PK study, included GT1-infected participants who were noncirrhotic and treatment-naïve (TN). Part 2, the safety and efficacy study, included GT1 or GT4-infected participants who were TN or interferon ([IFN] or Pegylated-interferon alfa-2a or 2b [pegIFN] with or without RBV) treatment-experienced (TE) without cirrhosis or with compensated cirrhosis. In Part 1 and Part 2, the treatment regimen and duration were dependent on HCV GT, GT1 subtype, and cirrhosis status.

Study Design

• Study Type: Interventional
• Actual Enrollment: 64 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: An Open-Label, Multicenter Study to Evaluate the Pharmacokinetics, Safety, and Efficacy of Ombitasvir (OBV), Paritaprevir (PTV), Ritonavir (RTV) With or Without Dasabuvir (DSV) and With or Without Ribavirin (RBV) in Pediatric Subjects With Genotype 1 or 4 Chronic Hepatitis C Virus (HCV) Infection (ZIRCON)
• Actual Study Start Date: Oct 28, 2015
• Actual Primary Completion Date: Nov 19, 2020
• Actual Study Completion Date: Nov 19, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Adult tablet, 12-17 yr, Part 1 Participants with HCV GT1b without cirrhosis received the adult 3-DAA (OBV/PTV/RTV and DSV) regimen: two 12.5 mg ombitasvir /75 mg paritaprevir /50 mg ritonavir tablets taken orally every morning (QD) and one dasabuvir 250 mg tablet taken orally twice a day (BID) for 12 weeks. Participants with HCV GT1a without cirrhosis received 12-week treatment with the adult 3-DAA regimen and ribavirin 200 mg tablets were administered orally per local label.	Drug: Ombitasvir/paritaprevir/ritonavir; Film-coated tablet for oral use; Other Names: Ombitasvir also known as ABT-267 Paritaprevir also known as ABT-450 Ombitsvir/paritaprevir/ritonavir also known as Viekirax ; Drug: Dasabuvir; Film-coated tablet for oral use; Other Names: Exviera ABT-333 ; Drug: Ribavirin; Film-coated tablet for oral use
Experimental: Adult tablet, 12-17 yr, Part 2 Participants with HCV GT1b received the adult 3-DAA (OBV/PTV/RTV and DSV) regimen: two 12.5 mg ombitasvir /75mg paritaprevir /50 mg ritonavir tablets taken orally every morning (QD) and one dasabuvir 250 mg tablet taken orally twice a day (BID) for 12 weeks. Participants with HCV GT1a without cirrhosis received 12-week treatment with the adult 3-DAA regimen and ribavirin 200 mg tablets were administered orally per local label. Participants with HCV GT1a with compensated cirrhosis received 24-week treatment with the adult 3-DAA regimen and ribavirin 200 mg tablets were administered orally per local label. Participants with HCV GT4 received 12-week treatment with the OBV/PTV/RTV formulation and ribavirin 200 mg tablets were administered orally per local label.	Drug: Ombitasvir/paritaprevir/ritonavir; Film-coated tablet for oral use; Other Names: Ombitasvir also known as ABT-267 Paritaprevir also known as ABT-450 Ombitsvir/paritaprevir/ritonavir also known as Viekirax ; Drug: Dasabuvir; Film-coated tablet for oral use; Other Names: Exviera ABT-333 ; Drug: Ribavirin; Film-coated tablet for oral use
Experimental: Mini tablet, 9-11 yr, Part 1 Participants with HCV GT1b without cirrhosis were to receive the mini-tablet 3-DAA (OBV, PTV, RTV, and DSV) regimen for 12 weeks: ombitasvir 0.3 mg, paritaprevir 1.0 mg, and ritonavir 1.0 mg mini-tablets administered orally QD based on body weight and dasabuvir taken orally BID as 3.08 mg mini-tablets based on body weight. Participants with HCV GT1a without cirrhosis received 12-week treatment with the mini-tablet 3-DAA regimen and ribavirin was provided as a 40 mg/mL oral solution and administered per local label.	Drug: Ombitasvir mini tablet; Film-coated tablet for oral use; Other Names: ABT-267 ; Drug: Paritaprevir mini tablet; Film-coated tablet for oral use; Other Names: ABT-450 ; Drug: Ritonavir mini tablet; Film-coated tablet for oral use; Drug: Dasabuvir mini tablet; Film-coated tablet for oral use; Other Names: Exviera ABT-333 ; Drug: Ribavirin solution; Oral solution
Experimental: Mini tablet, 3-8 yr, Part 1 Participants with HCV GT1b without cirrhosis were to receive the mini-tablet 3-DAA (OBV, PTV, RTV, and DSV) regimen for 12 weeks: ombitasvir 0.3 mg, paritaprevir 1.0 mg, and ritonavir 1.0 mg mini-tablets administered orally QD based on body weight and dasabuvir taken orally BID as 3.08 mg mini-tablets based on body weight. Participants with HCV GT1a without cirrhosis received 12-week treatment with the mini-tablet 3-DAA regimen and ribavirin was provided as a 40 mg/mL oral solution and administered per local label.	Drug: Ombitasvir mini tablet; Film-coated tablet for oral use; Other Names: ABT-267 ; Drug: Paritaprevir mini tablet; Film-coated tablet for oral use; Other Names: ABT-450 ; Drug: Ritonavir mini tablet; Film-coated tablet for oral use; Drug: Dasabuvir mini tablet; Film-coated tablet for oral use; Other Names: Exviera ABT-333 ; Drug: Ribavirin solution; Oral solution

Outcome Measures

Primary Outcome Measures

1. Part 1: Maximum Plasma Concentration (Cmax) of Ombitasvir (OBV) [At Week 2]

   Cmax is the peak concentration that a drug or drug metabolite achieves in a specified compartment after the drug has been administrated and before administration of a second dose.

2. Part 1: Concentration of Drug in Blood Plasma Over Time [Area Under the Curve (AUC)] of Ombitasvir (OBV) [At Week 2]

   AUC is a measure of how long and how much drug is present in the body after dosing. The amount of ombitasvir present was measured up to 24 hours after dosing.

3. Part 1: Lowest Plasma Concentration (Ctrough) of Ombitasvir (OBV) [At Weeks 2 and 8]

   Minimum plasma concentration (Ctrough; measured in ng/mL) was directly determined from the concentration-time data.

4. Part 1: Maximum Plasma Concentration (Cmax) of Paritaprevir (PTV) [At Week 2]

   Cmax is the peak concentration that a drug or drug metabolite achieves in a specified compartment after the drug has been administrated and before administration of a second dose.

5. Part 1: Concentration of Drug in Blood Plasma Over Time [Area Under the Curve (AUC)] of Paritaprevir (PTV) [At Week 2]

   AUC is a measure of how long and how much drug is present in the body after dosing. The amount of paritaprevir present was measured up to 24 hours after dosing.

6. Part 1: Lowest Plasma Concentration (Ctrough) of Paritaprevir (PTV) [At Weeks 2 and 8]

   Minimum plasma concentration (Ctrough; measured in ng/mL) was directly determined from the concentration-time data.

7. Part 1: Maximum Plasma Concentration (Cmax) of Dasabuvir (DSV) [At Week 2]

   Cmax is the peak concentration that a drug or drug metabolite achieves in a specified compartment after the drug has been administrated and before administration of a second dose.

8. Part 1: Concentration of Drug in Blood Plasma Against Time [Area Under the Curve (AUC)] of Dasabuvir (DSV) [At Week 2]

   AUC is a measure of how long and how much drug is present in the body after dosing. The amount of dasabuvir present was measured up to 12 hours after dosing. For two subjects in the 15-29 kg group, the 24 h concentration was used as the 12 h concentration due to the significant sampling time deviation. For one subject in the 30-44 kg group, the 24 h concentration was used as the 12 h concentration due to the significant sampling time deviation.

9. Part 1: Lowest Plasma Concentration (Ctrough) of Dasabuvir (DSV) [At Weeks 2 and 8]

   Minimum plasma concentration (Ctrough; measured in ng/mL) was directly determined from the concentration-time data.

10. Part 1: Maximum Plasma Concentration (Cmax) of Ritonavir (RTV) [At Week 2]

    Cmax is the peak concentration that a drug or drug metabolite achieves in a specified compartment after the drug has been administrated and before administration of a second dose.

11. Part 1: Concentration of Drug in Blood Plasma Over Time [Area Under the Curve (AUC)] of Ritonavir (RTV) [At Week 2]

    AUC is a measure of how long and how much drug is present in the body after dosing. The amount of ritonavir present was measured up to 24 hours after dosing.

12. Part 1: Lowest Plasma Concentration (Ctrough) of Ritonavir (RTV) [At Weeks 2 and 8]

    Minimum plasma concentration (Ctrough; measured in ng/mL) was directly determined from the concentration-time data.

13. Parts 1 and 2: Percentage of Participants With Sustained Virologic Response 12 Weeks After the Last Actual Dose of Study Drug (SVR12) [12 weeks after last dose of study drug (Week 24 or 36 depending on treatment duration)]

    SVR12 is defined as hepatitis C virus ribonucleic acid (HCV RNA) < lower limit of quantification (LLOQ) 12 weeks after the last actual dose of study drug.

Secondary Outcome Measures

1. Parts 1 and 2: Percentage of Participants With Sustained Virologic Response 12 Weeks After the Last Actual Dose of Study Drug (SVR12) Summarized by Formulation, Age and Weight Group, and Across All Subjects on the Adult Formulations [12 weeks after last dose of study drug (Week 24 or 36 depending on treatment duration)]

   SVR12 is defined as hepatitis C virus ribonucleic acid (HCV RNA) < lower limit of quantification (LLOQ) 12 weeks after the last actual dose of study drug.

2. Parts 1 & 2: Percentage of Participants With Sustained Virologic Response 24 Weeks After the Last Actual Dose of Study Drug (SVR24), Summarized by Formulation, Age and Weight Group, Across All Subjects, and Across All Subjects on the Adult Formulations [24 weeks after last dose of study drug (Week 36 or 48 depending on treatment duration)]

   SVR24 is defined as hepatitis C virus ribonucleic acid (HCV RNA) < lower limit of quantification (LLOQ) 24 weeks after the last actual dose of study drug.

3. Parts 1 and 2: Percentage of Participants With Alanine Aminotransferase (ALT) Normalization During Treatment by Formulation, Age and Weight Group, Across All Subjects, and Across All Subjects on the Adult Formulations [12 or 24 weeks after starting study drug, depending on treatment duration]

   Alanine aminotransferase (ALT) normalization during treatment is defined as ALT ≤ the upper limit of normal (ULN) at the final treatment visit for participants with ALT > ULN at baseline.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 3 Years to 17 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Positive anti-hepatitis C virus antibody (HCV Ab) and HCV ribonucleic acid (RNA) ≥ 1000 IU/mL at the time of screening

2. HCV genotype 1 for enrollment into Part 1 of the study and genotype 1 or 4 for enrollment into Part 2

3. Parent or legal guardian with the willingness and ability to provide written informed consent and participant willing and able to give assent, as appropriate for age and country

Exclusion Criteria:

1. Female participant who is pregnant, breastfeeding or is considering becoming pregnant

2. Use of known strong inducers and inhibitors (e.g., gemfibrozil) of cytochrome P450 2C8 (CYP2C8) in participants receiving dasabuvir, or strong or moderate inducers of CYP3A, within 2 weeks or 10 half-lives, whichever is longer, of the respective medication/supplement prior to study drug administration.

3. Positive test result for Hepatitis B surface antigen (HbsAg) or anti-human immunodeficiency virus antibody (HIV Ab) test

4. Current enrollment in another interventional clinical study, previous enrollment in this study, prior or current use of any investigational or commercially available anti-HCV agents other than interferons or ribavirin or receipt of any investigational product within 6 weeks prior to study drug administration

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	UCSF Benioff Childrens Hosp /ID# 136774	San Francisco	California	United States	94158
2	Children's Hospital Colorado /ID# 137017	Aurora	Colorado	United States	80045
3	University of Florida - Archer /ID# 136830	Gainesville	Florida	United States	32610
4	Advent Health /ID# 167663	Orlando	Florida	United States	32803
5	Indiana University /ID# 137015	Indianapolis	Indiana	United States	46202
6	Boston Childrens Hospital /ID# 137174	Boston	Massachusetts	United States	02115
7	Boston Medical Center /ID# 136831	Boston	Massachusetts	United States	02118
8	Columbia Univ Medical Center /ID# 136431	New York	New York	United States	10032-3725
9	Children's Hospital of Philadelphia /ID# 137018	Philadelphia	Pennsylvania	United States	19104
10	Baylor College of Medicine /ID# 136590	Houston	Texas	United States	77030-3411
11	Seattle Children's Hospital /ID# 137019	Seattle	Washington	United States	98105
12	Cliniques Universitaires Saint-Luc /ID# 136910	Brussels	Bruxelles-Capitale	Belgium	1200
13	UZ Leuven /ID# 136911	Leuven		Belgium	3000
14	Charite Universitaetsmedizin Berlin /ID# 141620	Berlin		Germany	10117
15	Universitaetsklinikum Freiburg /ID# 141618	Freiburg		Germany	79106
16	Helios Klinikum Wuppertal /ID# 142883	Wuppertal		Germany	42283
17	San Jorge Children Hospital /ID# 136832	San Juan		Puerto Rico	00912-3310
18	Hospital Sant Joan de Deu /ID# 137096	Esplugues de Llobregat	Barcelona	Spain	08950
19	Hospital Universitario Vall d'Hebron /ID# 137098	Barcelona		Spain	08035
20	Hospital Universitario La Paz /ID# 137094	Madrid		Spain	28046
21	Hospital Universitario y Politecnico La Fe /ID# 137097	Valencia		Spain	46026

Sponsors and Collaborators

• AbbVie

Investigators

• Study Director: AbbVie Inc., AbbVie

Study Documents (Full-Text)

• Study Protocol - Aug 21, 2017
• Statistical Analysis Plan - May 31, 2018

More Information

Publications

None provided.

• Responsible Party: AbbVie
• ClinicalTrials.gov Identifier: NCT02486406
• Other Study ID Numbers: M14-748; 2015-000111-41
• First Posted: Jul 1, 2015
• Last Update Posted: Oct 5, 2021
• Last Verified: Sep 1, 2021

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No
• Keywords provided by AbbVie: Hepatitis C Virus; Hepatitis C Genotype 1; Hepatitis C Genotype 4; Pediatric
• Additional relevant MeSH terms: Infections; Communicable Diseases; Hepatitis A; Hepatitis C; Hepatitis C, Chronic; Hepatitis; Hepatitis, Chronic; Ritonavir; Ribavirin

Study Results

Participant Flow

Pre-assignment Detail	Safety population: all participants who received at least one dose of study drug in Part 1 or Part 2

Arm/Group Title	Adult Tablet, 12-17 yr, Part 1	Adult Tablet, 12-17 yr, Part 2	Mini Tablet, 9-11 yr, Part 1	Mini Tablet, 3-8 yr, Part 1
Arm/Group Description	Participants with HCV GT1b without cirrhosis received the adult 3-DAA (OBV/PTV/RTV and DSV) regimen: two 12.5 mg ombitasvir /75 mg paritaprevir /50 mg ritonavir tablets taken orally every morning (QD) and one dasabuvir 250 mg tablet taken orally twice a day (BID) for 12 weeks. Participants with HCV GT1a without cirrhosis received 12-week treatment with the adult 3-DAA regimen and ribavirin 200 mg tablets were administered orally per local label.	Participants with HCV GT1b received the adult 3-DAA (OBV/PTV/RTV and DSV) regimen: two 12.5 mg ombitasvir /75mg paritaprevir /50 mg ritonavir tablets taken orally every morning (QD) and one dasabuvir 250 mg tablet taken orally twice a day (BID) for 12 weeks. Participants with HCV GT1a without cirrhosis received 12-week treatment with the adult 3-DAA regimen and ribavirin 200 mg tablets were administered orally per local label. Participants with HCV GT1a with compensated cirrhosis received 24-week treatment with the adult 3-DAA regimen and ribavirin 200 mg tablets were administered orally per local label. Participants with HCV GT4 received 12-week treatment with the OBV/PTV/RTV formulation and ribavirin 200 mg tablets were administered orally per local label.	Participants with HCV GT1b without cirrhosis were to receive the mini-tablet 3-DAA (OBV, PTV, RTV, and DSV) regimen for 12 weeks: ombitasvir 0.3 mg, paritaprevir 1.0 mg, and ritonavir 1.0 mg mini-tablets administered orally QD based on body weight and dasabuvir taken orally BID as 3.08 mg mini-tablets based on body weight. Participants with HCV GT1a without cirrhosis received 12-week treatment with the mini-tablet 3-DAA regimen and ribavirin was provided as a 40 mg/mL oral solution and administered per local label.	Participants with HCV GT1b without cirrhosis were to receive the mini-tablet 3-DAA (OBV, PTV, RTV, and DSV) regimen for 12 weeks: ombitasvir 0.3 mg, paritaprevir 1.0 mg, and ritonavir 1.0 mg mini-tablets administered orally QD based on body weight and dasabuvir taken orally BID as 3.08 mg mini-tablets based on body weight. Participants with HCV GT1a without cirrhosis received 12-week treatment with the mini-tablet 3-DAA regimen and ribavirin was provided as a 40 mg/mL oral solution and administered per local label.
Period Title: Overall Study
STARTED	12	26	12	14
COMPLETED	10	23	10	10
NOT COMPLETED	2	3	2	4

Baseline Characteristics

Arm/Group Title	Adult Tablet, 12-17 yr, Part 1	Adult Tablet, 12-17 yr, Part 2	Mini Tablet, 9-11 yr, Part 1	Mini Tablet, 3-8 yr, Part 1	Total
Arm/Group Description	Participants with HCV GT1b without cirrhosis received the adult 3-DAA (OBV/PTV/RTV and DSV) regimen: two 12.5 mg ombitasvir /75 mg paritaprevir /50 mg ritonavir tablets taken orally every morning (QD) and one dasabuvir 250 mg tablet taken orally twice a day (BID) for 12 weeks. Participants with HCV GT1a without cirrhosis received 12-week treatment with the adult 3-DAA regimen and ribavirin 200 mg tablets were administered orally per local label.	Participants with HCV GT1b received the adult 3-DAA (OBV/PTV/RTV and DSV) regimen: two 12.5 mg ombitasvir /75mg paritaprevir /50 mg ritonavir tablets taken orally every morning (QD) and one dasabuvir 250 mg tablet taken orally twice a day (BID) for 12 weeks. Participants with HCV GT1a without cirrhosis received 12-week treatment with the adult 3-DAA regimen and ribavirin 200 mg tablets were administered orally per local label. Participants with HCV GT1a with compensated cirrhosis received 24-week treatment with the adult 3-DAA regimen and ribavirin 200 mg tablets were administered orally per local label. Participants with HCV GT4 received 12-week treatment with the OBV/PTV/RTV formulation and ribavirin 200 mg tablets were administered orally per local label.	Participants with HCV GT1b without cirrhosis were to receive the mini-tablet 3-DAA (OBV, PTV, RTV, and DSV) regimen for 12 weeks: ombitasvir 0.3 mg, paritaprevir 1.0 mg, and ritonavir 1.0 mg mini-tablets administered orally QD based on body weight and dasabuvir taken orally BID as 3.08 mg mini-tablets based on body weight. Participants with HCV GT1a without cirrhosis received 12-week treatment with the mini-tablet 3-DAA regimen and ribavirin was provided as a 40 mg/mL oral solution and administered per local label.	Participants with HCV GT1b without cirrhosis were to receive the mini-tablet 3-DAA (OBV, PTV, RTV, and DSV) regimen for 12 weeks: ombitasvir 0.3 mg, paritaprevir 1.0 mg, and ritonavir 1.0 mg mini-tablets administered orally QD based on body weight and dasabuvir taken orally BID as 3.08 mg mini-tablets based on body weight. Participants with HCV GT1a without cirrhosis received 12-week treatment with the mini-tablet 3-DAA regimen and ribavirin was provided as a 40 mg/mL oral solution and administered per local label.	Total of all reporting groups
Overall Participants	12	26	12	14	64
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	15.4 (1.73)	15.0 (1.68)	9.8 (0.83)	4.8 (1.67)	11.9 (4.54)
Sex: Female, Male (Count of Participants)
Female	9 75%	16 61.5%	6 50%	11 78.6%	42 65.6%
Male	3 25%	10 38.5%	6 50%	3 21.4%	22 34.4%
Race/Ethnicity, Customized (Count of Participants)
White	6 50%	23 88.5%	10 83.3%	10 71.4%	49 76.6%
Black or African American	2 16.7%	3 11.5%	0 0%	4 28.6%	9 14.1%
Asian	3 25%	0 0%	1 8.3%	0 0%	4 6.3%
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%	0 0%
Multi race	1 8.3%	0 0%	1 8.3%	0 0%	2 3.1%

Outcome Measures

1. Primary Outcome

Title	Part 1: Maximum Plasma Concentration (Cmax) of Ombitasvir (OBV)
Description	Cmax is the peak concentration that a drug or drug metabolite achieves in a specified compartment after the drug has been administrated and before administration of a second dose.
Time Frame	At Week 2

Outcome Measure Data

Analysis Population Description

Intention-to-treat population: all participants who received at least one dose of study drug in Part 1 with available data

Arm/Group Title	15 - 29 kg Body Weight	30 - 44 kg Body Weight	≥ 45 kg Body Weight
Arm/Group Description	Participants in Part 1 of the study who weighed between 15-29 kg at the time of enrollment	Participants in Part 1 of the study who weighed between 30-44 kg at the time of enrollment	Participants in Part 1 of the study who weighed ≥ 45 kg at the time of enrollment
Measure Participants	12	9	13
Geometric Mean (Geometric Coefficient of Variation) [ng/mL]	99.6 (27)	116 (14)	83.7 (39)

2. Primary Outcome

Title	Part 1: Concentration of Drug in Blood Plasma Over Time [Area Under the Curve (AUC)] of Ombitasvir (OBV)
Description	AUC is a measure of how long and how much drug is present in the body after dosing. The amount of ombitasvir present was measured up to 24 hours after dosing.
Time Frame	At Week 2

Outcome Measure Data

Analysis Population Description

Intention-to-treat population: all participants who received at least one dose of study drug in Part 1 with available data

Arm/Group Title	15 - 29 kg Body Weight	30 - 44 kg Body Weight	≥ 45 kg Body Weight
Arm/Group Description	Participants in Part 1 of the study who weighed between 15-29 kg at the time of enrollment	Participants in Part 1 of the study who weighed between 30-44 kg at the time of enrollment	Participants in Part 1 of the study who weighed ≥ 45 kg at the time of enrollment
Measure Participants	12	8	12
Geometric Mean (Geometric Coefficient of Variation) [ng•h/mL]	1270 (26)	1490 (12)	1060 (43)

3. Primary Outcome

Title	Part 1: Lowest Plasma Concentration (Ctrough) of Ombitasvir (OBV)
Description	Minimum plasma concentration (Ctrough; measured in ng/mL) was directly determined from the concentration-time data.
Time Frame	At Weeks 2 and 8

Outcome Measure Data

Analysis Population Description

Intention-to-treat population: all participants who received at least one dose of study drug in Part 1 with available data

Arm/Group Title	15 - 29 kg Body Weight	30 - 44 kg Body Weight	≥ 45 kg Body Weight
Arm/Group Description	Participants in Part 1 of the study who weighed between 15-29 kg at the time of enrollment	Participants in Part 1 of the study who weighed between 30-44 kg at the time of enrollment	Participants in Part 1 of the study who weighed ≥ 45 kg at the time of enrollment
Measure Participants	12	8	12
Week 2	24.7 (32)	28.2 (16)	21.8 (39)
Week 8	29.6 (78)	30.4 (24)	20.9 (58)

4. Primary Outcome

Title	Part 1: Maximum Plasma Concentration (Cmax) of Paritaprevir (PTV)
Description	Cmax is the peak concentration that a drug or drug metabolite achieves in a specified compartment after the drug has been administrated and before administration of a second dose.
Time Frame	At Week 2

Outcome Measure Data

Analysis Population Description

Intention-to-treat population: all participants who received at least one dose of study drug in Part 1 with available data

Arm/Group Title	15 - 29 kg Body Weight	30 - 44 kg Body Weight	≥ 45 kg Body Weight
Arm/Group Description	Participants in Part 1 of the study who weighed between 15-29 kg at the time of enrollment	Participants in Part 1 of the study who weighed between 30-44 kg at the time of enrollment	Participants in Part 1 of the study who weighed ≥ 45 kg at the time of enrollment
Measure Participants	12	9	13
Geometric Mean (Geometric Coefficient of Variation) [ng/mL]	294 (152)	1540 (71)	870 (125)

5. Primary Outcome

Title	Part 1: Concentration of Drug in Blood Plasma Over Time [Area Under the Curve (AUC)] of Paritaprevir (PTV)
Description	AUC is a measure of how long and how much drug is present in the body after dosing. The amount of paritaprevir present was measured up to 24 hours after dosing.
Time Frame	At Week 2

Outcome Measure Data

Analysis Population Description

Intention-to-treat population: all participants who received at least one dose of study drug in Part 1 with available data

Arm/Group Title	15 - 29 kg Body Weight	30 - 44 kg Body Weight	≥ 45 kg Body Weight
Arm/Group Description	Participants in Part 1 of the study who weighed between 15-29 kg at the time of enrollment	Participants in Part 1 of the study who weighed between 30-44 kg at the time of enrollment	Participants in Part 1 of the study who weighed ≥ 45 kg at the time of enrollment
Measure Participants	12	8	12
Geometric Mean (Geometric Coefficient of Variation) [ng•h/mL]	2180 (136)	8640 (90)	5770 (152)

6. Primary Outcome

Title	Part 1: Lowest Plasma Concentration (Ctrough) of Paritaprevir (PTV)
Description	Minimum plasma concentration (Ctrough; measured in ng/mL) was directly determined from the concentration-time data.
Time Frame	At Weeks 2 and 8

Outcome Measure Data

Analysis Population Description

Intention-to-treat population: all participants who received at least one dose of study drug in Part 1 with available data

Arm/Group Title	15 - 29 kg Body Weight	30 - 44 kg Body Weight	≥ 45 kg Body Weight
Arm/Group Description	Participants in Part 1 of the study who weighed between 15-29 kg at the time of enrollment	Participants in Part 1 of the study who weighed between 30-44 kg at the time of enrollment	Participants in Part 1 of the study who weighed ≥ 45 kg at the time of enrollment
Measure Participants	12	8	12
Week 2	9.86 (113)	16.1 (112)	18.0 (78)
Week 8	17.3 (136)	18.4 (89)	23.5 (86)

7. Primary Outcome

Title	Part 1: Maximum Plasma Concentration (Cmax) of Dasabuvir (DSV)
Description	Cmax is the peak concentration that a drug or drug metabolite achieves in a specified compartment after the drug has been administrated and before administration of a second dose.
Time Frame	At Week 2

Outcome Measure Data

Analysis Population Description

Intention-to-treat population: all participants who received at least one dose of study drug in Part 1 with available data

Arm/Group Title	15 - 29 kg Body Weight	30 - 44 kg Body Weight	≥ 45 kg Body Weight
Arm/Group Description	Participants in Part 1 of the study who weighed between 15-29 kg at the time of enrollment	Participants in Part 1 of the study who weighed between 30-44 kg at the time of enrollment	Participants in Part 1 of the study who weighed ≥ 45 kg at the time of enrollment
Measure Participants	12	9	13
Geometric Mean (Geometric Coefficient of Variation) [ng/mL]	579 (44)	830 (45)	671 (48)

8. Primary Outcome

Title	Part 1: Concentration of Drug in Blood Plasma Against Time [Area Under the Curve (AUC)] of Dasabuvir (DSV)
Description	AUC is a measure of how long and how much drug is present in the body after dosing. The amount of dasabuvir present was measured up to 12 hours after dosing. For two subjects in the 15-29 kg group, the 24 h concentration was used as the 12 h concentration due to the significant sampling time deviation. For one subject in the 30-44 kg group, the 24 h concentration was used as the 12 h concentration due to the significant sampling time deviation.
Time Frame	At Week 2

Outcome Measure Data

Analysis Population Description

Intention-to-treat population: all participants who received at least one dose of study drug in Part 1 with available data

Arm/Group Title	15 - 29 kg Body Weight	30 - 44 kg Body Weight	≥ 45 kg Body Weight
Arm/Group Description	Participants in Part 1 of the study who weighed between 15-29 kg at the time of enrollment	Participants in Part 1 of the study who weighed between 30-44 kg at the time of enrollment	Participants in Part 1 of the study who weighed ≥ 45 kg at the time of enrollment
Measure Participants	12	9	13
Geometric Mean (Geometric Coefficient of Variation) [ng•h/mL]	3960 (44)	5960 (47)	4630 (49)

9. Primary Outcome

Title	Part 1: Lowest Plasma Concentration (Ctrough) of Dasabuvir (DSV)
Description	Minimum plasma concentration (Ctrough; measured in ng/mL) was directly determined from the concentration-time data.
Time Frame	At Weeks 2 and 8

Outcome Measure Data

Analysis Population Description

Intention-to-treat population: all participants who received at least one dose of study drug in Part 1 with available data

Arm/Group Title	15 - 29 kg Body Weight	30 - 44 kg Body Weight	≥ 45 kg Body Weight
Arm/Group Description	Participants in Part 1 of the study who weighed between 15-29 kg at the time of enrollment	Participants in Part 1 of the study who weighed between 30-44 kg at the time of enrollment	Participants in Part 1 of the study who weighed ≥ 45 kg at the time of enrollment
Measure Participants	12	9	13
Week 2	110 (57)	215 (54)	165 (56)
Week 8	168 (82)	264 (65)	191 (60)

10. Primary Outcome

Title	Part 1: Maximum Plasma Concentration (Cmax) of Ritonavir (RTV)
Description	Cmax is the peak concentration that a drug or drug metabolite achieves in a specified compartment after the drug has been administrated and before administration of a second dose.
Time Frame	At Week 2

Outcome Measure Data

Analysis Population Description

Intention-to-treat population: all participants who received at least one dose of study drug in Part 1 with available data

Arm/Group Title	15 - 29 kg Body Weight	30 - 44 kg Body Weight	≥ 45 kg Body Weight
Arm/Group Description	Participants in Part 1 of the study who weighed between 15-29 kg at the time of enrollment	Participants in Part 1 of the study who weighed between 30-44 kg at the time of enrollment	Participants in Part 1 of the study who weighed ≥ 45 kg at the time of enrollment
Measure Participants	12	9	13
Geometric Mean (Geometric Coefficient of Variation) [ng/mL]	1090 (67)	1830 (42)	1180 (35)

11. Primary Outcome

Title	Part 1: Concentration of Drug in Blood Plasma Over Time [Area Under the Curve (AUC)] of Ritonavir (RTV)
Description	AUC is a measure of how long and how much drug is present in the body after dosing. The amount of ritonavir present was measured up to 24 hours after dosing.
Time Frame	At Week 2

Outcome Measure Data

Analysis Population Description

Intention-to-treat population: all participants who received at least one dose of study drug in Part 1 with available data

Arm/Group Title	15 - 29 kg Body Weight	30 - 44 kg Body Weight	≥ 45 kg Body Weight
Arm/Group Description	Participants in Part 1 of the study who weighed between 15-29 kg at the time of enrollment	Participants in Part 1 of the study who weighed between 30-44 kg at the time of enrollment	Participants in Part 1 of the study who weighed ≥ 45 kg at the time of enrollment
Measure Participants	12	9	12
Geometric Mean (Geometric Coefficient of Variation) [ng•h/mL]	6570 (60)	14100 (49)	8900 (37)

12. Primary Outcome

Title	Part 1: Lowest Plasma Concentration (Ctrough) of Ritonavir (RTV)
Description	Minimum plasma concentration (Ctrough; measured in ng/mL) was directly determined from the concentration-time data.
Time Frame	At Weeks 2 and 8

Outcome Measure Data

Analysis Population Description

Intention-to-treat population: all participants who received at least one dose of study drug in Part 1 with available data

Arm/Group Title	15 - 29 kg Body Weight	30 - 44 kg Body Weight	≥ 45 kg Body Weight
Arm/Group Description	Participants in Part 1 of the study who weighed between 15-29 kg at the time of enrollment	Participants in Part 1 of the study who weighed between 30-44 kg at the time of enrollment	Participants in Part 1 of the study who weighed ≥ 45 kg at the time of enrollment
Measure Participants	12	9	12
Week 2	16.1 (72)	32.1 (63)	29.8 (54)
Week 8	91.8 (268)	38.1 (112)	58.2 (138)

13. Primary Outcome

Title	Parts 1 and 2: Percentage of Participants With Sustained Virologic Response 12 Weeks After the Last Actual Dose of Study Drug (SVR12)
Description	SVR12 is defined as hepatitis C virus ribonucleic acid (HCV RNA) < lower limit of quantification (LLOQ) 12 weeks after the last actual dose of study drug.
Time Frame	12 weeks after last dose of study drug (Week 24 or 36 depending on treatment duration)

Outcome Measure Data

Analysis Population Description

Intention-to-treat population: all participants who received at least one dose of study drug in Part 1 or 2; those with missing data after backwards imputation were treated as nonresponders

Arm/Group Title	All Participants, Total
Arm/Group Description	All participants who received at least one dose of study drug in Part 1 or Part 2
Measure Participants	64
Number (95% Confidence Interval) [percentage of participants]	98.4 820%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	15 - 29 kg Body Weight
	Comments	According to the Highlights of Prescribing Information of PEGASYS, the SVR24 rate was 47% among 45 treatment-naïve pediatric participants with HCV GT1 in the NV17424 trial. To show that the DAA regimen is superior to this current standard of care by 20%, the lower bound of the 2-sided 95% confidence interval of the SVR12 rate across all participants in the study must be greater than 67%.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Wilson's score method
	Estimated Value	98.4
	Confidence Interval	(2-Sided) 95%; 91.7 to 99.7
	Parameter Dispersion	Type: Value:
	Estimation Comments

14. Secondary Outcome

Title	Parts 1 and 2: Percentage of Participants With Sustained Virologic Response 12 Weeks After the Last Actual Dose of Study Drug (SVR12) Summarized by Formulation, Age and Weight Group, and Across All Subjects on the Adult Formulations
Description	SVR12 is defined as hepatitis C virus ribonucleic acid (HCV RNA) < lower limit of quantification (LLOQ) 12 weeks after the last actual dose of study drug.
Time Frame	12 weeks after last dose of study drug (Week 24 or 36 depending on treatment duration)

Outcome Measure Data

Analysis Population Description

Intention-to-treat population: all participants who received at least one dose of study drug in Part 1 or 2; those with missing data after backwards imputation were treated as nonresponders

Arm/Group Title	Adult Tablet, 12-17 YR, ≥ 45 kg	Mini-tablet, 9-11 YR, 15 to 29 kg	Mini-tablet, 9-11 YR, 30 to 44 kg	Mini-tablet, 9-11 YR, ≥ 45 kg	Mini-tablet, 3-8 YR, 15 to 29 kg	Mini-tablet Total
Arm/Group Description	Participants age 12-17 years old who received the adult formulation and weighed ≥ 45 kg	Participants age 9-11 years old who received the mini-tablet formulation and weighed 15 to 29 kg	Participants age 9-11 years old who received the mini-tablet formulation and weighed 30 to 44 kg	Participants age 9-11 years old who received the mini-tablet formulation and weighed ≥ 45 kg	Participants age 3-8 years old who received the mini-tablet formulation and weighed 15 to 29 kg	All participants who received the mini-tablet formulation
Measure Participants	38	1	9	2	14	26
Number (95% Confidence Interval) [percentage of participants]	100 833.3%	100 384.6%	100 833.3%	100 714.3%	92.9 145.2%	96.2 NaN

15. Secondary Outcome

Title	Parts 1 & 2: Percentage of Participants With Sustained Virologic Response 24 Weeks After the Last Actual Dose of Study Drug (SVR24), Summarized by Formulation, Age and Weight Group, Across All Subjects, and Across All Subjects on the Adult Formulations
Description	SVR24 is defined as hepatitis C virus ribonucleic acid (HCV RNA) < lower limit of quantification (LLOQ) 24 weeks after the last actual dose of study drug.
Time Frame	24 weeks after last dose of study drug (Week 36 or 48 depending on treatment duration)

Outcome Measure Data

Analysis Population Description

Intention-to-treat population: all participants who received at least one dose of study drug in Part 1 or 2; those with missing data after backwards imputation were treated as nonresponders

Arm/Group Title	Participants in Parts 1 and 2 of the Study	Adult Tablet, 12-17 YR, ≥ 45 kg	Mini-tablet, 9-11 YR, 15 to 29 kg	Mini-tablet, 9-11 YR, 30 to 44 kg	Mini-tablet, 9-11 YR, ≥ 45 kg	Mini-tablet, 3-8 YR, 15 to 29 kg	Mini-tablet Total
Arm/Group Description	Participants in Parts 1 and 2 who were part of the ITT population (those who received at least one dose of study drug in Part 1 or Part 2)	Participants age 12-17 years old who received the adult formulation and weighed ≥ 45 kg	Participants age 9-11 years old who received the mini-tablet formulation and weighed 15 to 29 kg	Participants age 9-11 years old who received the mini-tablet formulation and weighed 30 to 44 kg	Participants age 9-11 years old who received the mini-tablet formulation and weighed ≥ 45 kg	Participants age 3-8 years old who received the mini-tablet formulation and weighed 15 to 29 kg	All participants who received the mini-tablet formulation
Measure Participants	64	38	1	9	2	14	26
Number (95% Confidence Interval) [percentage of participants]	96.9 807.5%	100 384.6%	100.0 833.3%	88.9 635%	100.0 156.3%	92.9 NaN	92.3 NaN

16. Secondary Outcome

Title	Parts 1 and 2: Percentage of Participants With Alanine Aminotransferase (ALT) Normalization During Treatment by Formulation, Age and Weight Group, Across All Subjects, and Across All Subjects on the Adult Formulations
Description	Alanine aminotransferase (ALT) normalization during treatment is defined as ALT ≤ the upper limit of normal (ULN) at the final treatment visit for participants with ALT > ULN at baseline.
Time Frame	12 or 24 weeks after starting study drug, depending on treatment duration

Outcome Measure Data

Analysis Population Description

Intention-to-treat population including participants whose alanine aminotransferase (ALT) levels were > the upper limit of normal at baseline and who had available on-treatment ALT data

Arm/Group Title	Adult Tablet,12-17 YR, ≥ 45 kg, ALT Normalization	Mini-tablet, 9-11 YR, 15 to 29 kg, ALT Normalization	Mini-tablet, 9-11 YR, 30 to 44 kg, ALT Normalization	Mini-tablet, 3-8 YR, 15 to 29 kg, ALT Normalization	Mini-tablet Total, ALT Normalization	Participants in Parts 1 and 2 of the Study, ALT Normalization
Arm/Group Description	Participants age 12-17 years old with alanine aminotransferase > upper limit of normal at baseline who received the adult formulation and weighed ≥ 45 kg	Participants age 9-11 years old with alanine aminotransferase > upper limit of normal at baseline who received the mini-tablet formulation and weighed 15 to 29 kg	Participants age 9-11 years old with alanine aminotransferase > upper limit of normal at baseline who received the mini-tablet formulation and weighed 30 to 44 kg	Participants age 3-8 years old with alanine aminotransferase > upper limit of normal at baseline who received the mini-tablet formulation and weighed 15 to 29 kg	All participants with alanine aminotransferase > upper limit of normal at baseline who received the mini-tablet formulation	All participants with alanine aminotransferase > upper limit of normal at baseline
Measure Participants	24	1	5	10	16	40
Number (95% Confidence Interval) [percentage of participants]	87.5 729.2%	100 384.6%	100 833.3%	80.0 571.4%	87.5 136.7%	87.5 NaN

Adverse Events

Time Frame	Treatment-emergent adverse events (TEAEs) and serious adverse events (TESAEs) were collected from the first dose of study drug until 30 days after last dose, up to 37 weeks. SAEs and protocol-related nonserious AEs were collected from the time the subject signed consent.
Adverse Event Reporting Description	TEAEs and SAEs are defined as any AE or SAE with onset or worsening reported by a participant from the time that the first dose of study drug is administered until 30 days have elapsed following discontinuation of study drug. TEAEs were collected whether elicited or spontaneously reported by the participant.
Arm/Group Title	Adult Tablet, 12-17 yr, Part 1		Adult Tablet, 12-17 yr, Part 2		Adult Tablet, 12-17 yr, Total		Mini Tablet, 9-11 yr, Part 1		Mini Tablet, 3-8 yr, Part 1		Mini Tablet, Total		All Participants, Total
Arm/Group Description	Participants with HCV GT1b without cirrhosis received the adult 3-DAA (OBV/PTV/RTV and DSV) regimen: two 12.5 mg ombitasvir /75 mg paritaprevir /50 mg ritonavir tablets taken orally every morning (QD) and one dasabuvir 250 mg tablet taken orally twice a day (BID) for 12 weeks. Participants with HCV GT1a without cirrhosis received 12-week treatment with the adult 3-DAA regimen and ribavirin 200 mg tablets were administered orally per local label.		Participants with HCV GT1b received the adult 3-DAA (OBV/PTV/RTV and DSV) regimen: two 12.5 mg ombitasvir /75mg paritaprevir /50 mg ritonavir tablets taken orally every morning (QD) and one dasabuvir 250 mg tablet taken orally twice a day (BID) for 12 weeks. Participants with HCV GT1a without cirrhosis received 12-week treatment with the adult 3-DAA regimen and ribavirin 200 mg tablets were administered orally per local label. Participants with HCV GT1a with compensated cirrhosis received 24-week treatment with the adult 3-DAA regimen and ribavirin 200 mg tablets were administered orally per local label. Participants with HCV GT4 received 12-week treatment with the OBV/PTV/RTV formulation and ribavirin 200 mg tablets were administered orally per local label.		Participants age 12-17 years old who received at least one dose of the adult formulation		Participants with HCV GT1b without cirrhosis were to receive the mini-tablet 3-DAA (OBV, PTV, RTV, and DSV) regimen for 12 weeks: ombitasvir 0.3 mg, paritaprevir 1.0 mg, and ritonavir 1.0 mg mini-tablets administered orally QD based on body weight and dasabuvir taken orally BID as 3.08 mg mini-tablets based on body weight. Participants with HCV GT1a without cirrhosis received 12-week treatment with the mini-tablet 3-DAA regimen and ribavirin was provided as a 40 mg/mL oral solution and administered per local label.		Participants with HCV GT1b without cirrhosis were to receive the mini-tablet 3-DAA (OBV, PTV, RTV, and DSV) regimen for 12 weeks: ombitasvir 0.3 mg, paritaprevir 1.0 mg, and ritonavir 1.0 mg mini-tablets administered orally QD based on body weight and dasabuvir taken orally BID as 3.08 mg mini-tablets based on body weight. Participants with HCV GT1a without cirrhosis received 12-week treatment with the mini-tablet 3-DAA regimen and ribavirin was provided as a 40 mg/mL oral solution and administered per local label.		Participants who received at least one dose of the mini-tablet formulation		All participants who received at least one dose of study drug in Part 1 or Part 2
All Cause Mortality
	Adult Tablet, 12-17 yr, Part 1		Adult Tablet, 12-17 yr, Part 2		Adult Tablet, 12-17 yr, Total		Mini Tablet, 9-11 yr, Part 1		Mini Tablet, 3-8 yr, Part 1		Mini Tablet, Total		All Participants, Total
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/12 (0%)		0/26 (0%)		0/38 (0%)		0/12 (0%)		0/14 (0%)		0/26 (0%)		0/64 (0%)
Serious Adverse Events
	Adult Tablet, 12-17 yr, Part 1		Adult Tablet, 12-17 yr, Part 2		Adult Tablet, 12-17 yr, Total		Mini Tablet, 9-11 yr, Part 1		Mini Tablet, 3-8 yr, Part 1		Mini Tablet, Total		All Participants, Total
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/12 (0%)		0/26 (0%)		0/38 (0%)		1/12 (8.3%)		0/14 (0%)		1/26 (3.8%)		1/64 (1.6%)
Blood and lymphatic system disorders
Leukopenia	0/12 (0%)	0	0/26 (0%)	0	0/38 (0%)	0	1/12 (8.3%)	1	0/14 (0%)	0	1/26 (3.8%)	1	1/64 (1.6%)	1
Neutropenia	0/12 (0%)	0	0/26 (0%)	0	0/38 (0%)	0	1/12 (8.3%)	1	0/14 (0%)	0	1/26 (3.8%)	1	1/64 (1.6%)	1
Other (Not Including Serious) Adverse Events
	Adult Tablet, 12-17 yr, Part 1		Adult Tablet, 12-17 yr, Part 2		Adult Tablet, 12-17 yr, Total		Mini Tablet, 9-11 yr, Part 1		Mini Tablet, 3-8 yr, Part 1		Mini Tablet, Total		All Participants, Total
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	11/12 (91.7%)		17/26 (65.4%)		28/38 (73.7%)		12/12 (100%)		9/14 (64.3%)		21/26 (80.8%)		49/64 (76.6%)
Blood and lymphatic system disorders
Anaemia	1/12 (8.3%)	2	0/26 (0%)	0	1/38 (2.6%)	2	1/12 (8.3%)	1	0/14 (0%)	0	1/26 (3.8%)	1	2/64 (3.1%)	3
Haemolysis	0/12 (0%)	0	0/26 (0%)	0	0/38 (0%)	0	1/12 (8.3%)	1	0/14 (0%)	0	1/26 (3.8%)	1	1/64 (1.6%)	1
Lymphopenia	0/12 (0%)	0	0/26 (0%)	0	0/38 (0%)	0	1/12 (8.3%)	1	0/14 (0%)	0	1/26 (3.8%)	1	1/64 (1.6%)	1
Neutropenia	0/12 (0%)	0	0/26 (0%)	0	0/38 (0%)	0	1/12 (8.3%)	1	0/14 (0%)	0	1/26 (3.8%)	1	1/64 (1.6%)	1
Cardiac disorders
Atrioventricular block first degree	0/12 (0%)	0	0/26 (0%)	0	0/38 (0%)	0	1/12 (8.3%)	1	0/14 (0%)	0	1/26 (3.8%)	1	1/64 (1.6%)	1
Ear and labyrinth disorders
Vertigo	0/12 (0%)	0	0/26 (0%)	0	0/38 (0%)	0	1/12 (8.3%)	1	0/14 (0%)	0	1/26 (3.8%)	1	1/64 (1.6%)	1
Gastrointestinal disorders
Abdominal discomfort	0/12 (0%)	0	0/26 (0%)	0	0/38 (0%)	0	0/12 (0%)	0	1/14 (7.1%)	1	1/26 (3.8%)	1	1/64 (1.6%)	1
Abdominal pain	2/12 (16.7%)	2	0/26 (0%)	0	2/38 (5.3%)	2	1/12 (8.3%)	1	0/14 (0%)	0	1/26 (3.8%)	1	3/64 (4.7%)	3
Abdominal pain upper	0/12 (0%)	0	1/26 (3.8%)	1	1/38 (2.6%)	1	2/12 (16.7%)	2	0/14 (0%)	0	2/26 (7.7%)	2	3/64 (4.7%)	3
Constipation	0/12 (0%)	0	1/26 (3.8%)	1	1/38 (2.6%)	1	0/12 (0%)	0	1/14 (7.1%)	1	1/26 (3.8%)	1	2/64 (3.1%)	2
Diarrhoea	0/12 (0%)	0	1/26 (3.8%)	1	1/38 (2.6%)	1	3/12 (25%)	3	0/14 (0%)	0	3/26 (11.5%)	3	4/64 (6.3%)	4
Flatulence	0/12 (0%)	0	0/26 (0%)	0	0/38 (0%)	0	2/12 (16.7%)	2	0/14 (0%)	0	2/26 (7.7%)	2	2/64 (3.1%)	2
Gastritis	0/12 (0%)	0	1/26 (3.8%)	1	1/38 (2.6%)	1	1/12 (8.3%)	1	0/14 (0%)	0	1/26 (3.8%)	1	2/64 (3.1%)	2
Lip ulceration	1/12 (8.3%)	1	0/26 (0%)	0	1/38 (2.6%)	1	0/12 (0%)	0	0/14 (0%)	0	0/26 (0%)	0	1/64 (1.6%)	1
Nausea	3/12 (25%)	3	0/26 (0%)	0	3/38 (7.9%)	3	3/12 (25%)	3	1/14 (7.1%)	1	4/26 (15.4%)	4	7/64 (10.9%)	7
Vomiting	0/12 (0%)	0	1/26 (3.8%)	1	1/38 (2.6%)	1	4/12 (33.3%)	4	1/14 (7.1%)	1	5/26 (19.2%)	5	6/64 (9.4%)	6
General disorders
Chest discomfort	1/12 (8.3%)	1	0/26 (0%)	0	1/38 (2.6%)	1	0/12 (0%)	0	0/14 (0%)	0	0/26 (0%)	0	1/64 (1.6%)	1
Chest pain	1/12 (8.3%)	1	1/26 (3.8%)	1	2/38 (5.3%)	2	0/12 (0%)	0	0/14 (0%)	0	0/26 (0%)	0	2/64 (3.1%)	2
Chills	1/12 (8.3%)	1	0/26 (0%)	0	1/38 (2.6%)	1	0/12 (0%)	0	0/14 (0%)	0	0/26 (0%)	0	1/64 (1.6%)	1
Fatigue	2/12 (16.7%)	2	5/26 (19.2%)	5	7/38 (18.4%)	7	5/12 (41.7%)	5	1/14 (7.1%)	1	6/26 (23.1%)	6	13/64 (20.3%)	13
Influenza like illness	0/12 (0%)	0	0/26 (0%)	0	0/38 (0%)	0	0/12 (0%)	0	1/14 (7.1%)	1	1/26 (3.8%)	1	1/64 (1.6%)	1
Pain	0/12 (0%)	0	0/26 (0%)	0	0/38 (0%)	0	1/12 (8.3%)	1	1/14 (7.1%)	1	2/26 (7.7%)	2	2/64 (3.1%)	2
Pyrexia	2/12 (16.7%)	2	1/26 (3.8%)	1	3/38 (7.9%)	3	3/12 (25%)	4	2/14 (14.3%)	2	5/26 (19.2%)	6	8/64 (12.5%)	9
Vessel puncture site pain	0/12 (0%)	0	0/26 (0%)	0	0/38 (0%)	0	0/12 (0%)	0	1/14 (7.1%)	1	1/26 (3.8%)	1	1/64 (1.6%)	1
Hepatobiliary disorders
Hyperbilirubinaemia	0/12 (0%)	0	0/26 (0%)	0	0/38 (0%)	0	1/12 (8.3%)	1	0/14 (0%)	0	1/26 (3.8%)	1	1/64 (1.6%)	1
Immune system disorders
Seasonal allergy	0/12 (0%)	0	0/26 (0%)	0	0/38 (0%)	0	2/12 (16.7%)	2	0/14 (0%)	0	2/26 (7.7%)	2	2/64 (3.1%)	2
Infections and infestations
Acute sinusitis	0/12 (0%)	0	0/26 (0%)	0	0/38 (0%)	0	1/12 (8.3%)	1	0/14 (0%)	0	1/26 (3.8%)	1	1/64 (1.6%)	1
Gastroenteritis	0/12 (0%)	0	1/26 (3.8%)	1	1/38 (2.6%)	1	0/12 (0%)	0	1/14 (7.1%)	1	1/26 (3.8%)	1	2/64 (3.1%)	2
Gastroenteritis viral	0/12 (0%)	0	0/26 (0%)	0	0/38 (0%)	0	0/12 (0%)	0	2/14 (14.3%)	2	2/26 (7.7%)	2	2/64 (3.1%)	2
Impetigo	0/12 (0%)	0	1/26 (3.8%)	1	1/38 (2.6%)	1	0/12 (0%)	0	1/14 (7.1%)	1	1/26 (3.8%)	1	2/64 (3.1%)	2
Influenza	0/12 (0%)	0	1/26 (3.8%)	1	1/38 (2.6%)	1	1/12 (8.3%)	1	0/14 (0%)	0	1/26 (3.8%)	1	2/64 (3.1%)	2
Nasopharyngitis	1/12 (8.3%)	1	4/26 (15.4%)	5	5/38 (13.2%)	6	2/12 (16.7%)	2	1/14 (7.1%)	2	3/26 (11.5%)	4	8/64 (12.5%)	10
Oral herpes	1/12 (8.3%)	1	0/26 (0%)	0	1/38 (2.6%)	1	0/12 (0%)	0	0/14 (0%)	0	0/26 (0%)	0	1/64 (1.6%)	1
Otitis media	1/12 (8.3%)	1	0/26 (0%)	0	1/38 (2.6%)	1	0/12 (0%)	0	0/14 (0%)	0	0/26 (0%)	0	1/64 (1.6%)	1
Pharyngitis streptococcal	1/12 (8.3%)	1	0/26 (0%)	0	1/38 (2.6%)	1	1/12 (8.3%)	1	0/14 (0%)	0	1/26 (3.8%)	1	2/64 (3.1%)	2
Sinusitis	2/12 (16.7%)	2	0/26 (0%)	0	2/38 (5.3%)	2	0/12 (0%)	0	0/14 (0%)	0	0/26 (0%)	0	2/64 (3.1%)	2
Streptococcal infection	0/12 (0%)	0	0/26 (0%)	0	0/38 (0%)	0	0/12 (0%)	0	1/14 (7.1%)	1	1/26 (3.8%)	1	1/64 (1.6%)	1
Tracheitis	1/12 (8.3%)	1	0/26 (0%)	0	1/38 (2.6%)	1	0/12 (0%)	0	0/14 (0%)	0	0/26 (0%)	0	1/64 (1.6%)	1
Upper respiratory tract infection	2/12 (16.7%)	3	2/26 (7.7%)	3	4/38 (10.5%)	6	1/12 (8.3%)	1	3/14 (21.4%)	3	4/26 (15.4%)	4	8/64 (12.5%)	10
Viral infection	0/12 (0%)	0	0/26 (0%)	0	0/38 (0%)	0	1/12 (8.3%)	1	1/14 (7.1%)	1	2/26 (7.7%)	2	2/64 (3.1%)	2
Injury, poisoning and procedural complications
Arthropod bite	0/12 (0%)	0	0/26 (0%)	0	0/38 (0%)	0	1/12 (8.3%)	1	0/14 (0%)	0	1/26 (3.8%)	1	1/64 (1.6%)	1
Investigations
Blood bilirubin increased	0/12 (0%)	0	0/26 (0%)	0	0/38 (0%)	0	1/12 (8.3%)	1	0/14 (0%)	0	1/26 (3.8%)	1	1/64 (1.6%)	1
Electrocardiogram abnormal	0/12 (0%)	0	0/26 (0%)	0	0/38 (0%)	0	1/12 (8.3%)	1	0/14 (0%)	0	1/26 (3.8%)	1	1/64 (1.6%)	1
Electrocardiogram change	0/12 (0%)	0	0/26 (0%)	0	0/38 (0%)	0	1/12 (8.3%)	1	0/14 (0%)	0	1/26 (3.8%)	1	1/64 (1.6%)	1
Haemoglobin decreased	0/12 (0%)	0	0/26 (0%)	0	0/38 (0%)	0	1/12 (8.3%)	1	0/14 (0%)	0	1/26 (3.8%)	1	1/64 (1.6%)	1
Metabolism and nutrition disorders
Decreased appetite	1/12 (8.3%)	1	1/26 (3.8%)	1	2/38 (5.3%)	2	1/12 (8.3%)	1	0/14 (0%)	0	1/26 (3.8%)	1	3/64 (4.7%)	3
Hypertriglyceridaemia	0/12 (0%)	0	0/26 (0%)	0	0/38 (0%)	0	0/12 (0%)	0	1/14 (7.1%)	1	1/26 (3.8%)	1	1/64 (1.6%)	1
Increased appetite	0/12 (0%)	0	0/26 (0%)	0	0/38 (0%)	0	1/12 (8.3%)	1	0/14 (0%)	0	1/26 (3.8%)	1	1/64 (1.6%)	1
Musculoskeletal and connective tissue disorders
Arthralgia	1/12 (8.3%)	1	0/26 (0%)	0	1/38 (2.6%)	1	0/12 (0%)	0	0/14 (0%)	0	0/26 (0%)	0	1/64 (1.6%)	1
Back pain	1/12 (8.3%)	1	0/26 (0%)	0	1/38 (2.6%)	1	0/12 (0%)	0	0/14 (0%)	0	0/26 (0%)	0	1/64 (1.6%)	1
Musculoskeletal pain	1/12 (8.3%)	1	1/26 (3.8%)	1	2/38 (5.3%)	2	0/12 (0%)	0	0/14 (0%)	0	0/26 (0%)	0	2/64 (3.1%)	2
Neck pain	1/12 (8.3%)	1	1/26 (3.8%)	1	2/38 (5.3%)	2	0/12 (0%)	0	0/14 (0%)	0	0/26 (0%)	0	2/64 (3.1%)	2
Pain in extremity	1/12 (8.3%)	1	0/26 (0%)	0	1/38 (2.6%)	1	0/12 (0%)	0	0/14 (0%)	0	0/26 (0%)	0	1/64 (1.6%)	1
Pain in jaw	1/12 (8.3%)	1	0/26 (0%)	0	1/38 (2.6%)	1	0/12 (0%)	0	0/14 (0%)	0	0/26 (0%)	0	1/64 (1.6%)	1
Nervous system disorders
Dizziness	0/12 (0%)	0	2/26 (7.7%)	2	2/38 (5.3%)	2	0/12 (0%)	0	0/14 (0%)	0	0/26 (0%)	0	2/64 (3.1%)	2
Headache	3/12 (25%)	3	5/26 (19.2%)	5	8/38 (21.1%)	8	5/12 (41.7%)	6	2/14 (14.3%)	2	7/26 (26.9%)	8	15/64 (23.4%)	16
Paraesthesia	1/12 (8.3%)	2	0/26 (0%)	0	1/38 (2.6%)	2	0/12 (0%)	0	0/14 (0%)	0	0/26 (0%)	0	1/64 (1.6%)	2
Psychiatric disorders
Anxiety	2/12 (16.7%)	2	0/26 (0%)	0	2/38 (5.3%)	2	0/12 (0%)	0	0/14 (0%)	0	0/26 (0%)	0	2/64 (3.1%)	2
Behavioural insomnia of childhood	0/12 (0%)	0	0/26 (0%)	0	0/38 (0%)	0	0/12 (0%)	0	1/14 (7.1%)	1	1/26 (3.8%)	1	1/64 (1.6%)	1
Depression	0/12 (0%)	0	0/26 (0%)	0	0/38 (0%)	0	1/12 (8.3%)	1	0/14 (0%)	0	1/26 (3.8%)	1	1/64 (1.6%)	1
Mood swings	0/12 (0%)	0	0/26 (0%)	0	0/38 (0%)	0	1/12 (8.3%)	1	0/14 (0%)	0	1/26 (3.8%)	1	1/64 (1.6%)	1
Nightmare	0/12 (0%)	0	0/26 (0%)	0	0/38 (0%)	0	0/12 (0%)	0	1/14 (7.1%)	1	1/26 (3.8%)	1	1/64 (1.6%)	1
Sleep terror	0/12 (0%)	0	0/26 (0%)	0	0/38 (0%)	0	0/12 (0%)	0	1/14 (7.1%)	1	1/26 (3.8%)	1	1/64 (1.6%)	1
Suicidal ideation	0/12 (0%)	0	0/26 (0%)	0	0/38 (0%)	0	1/12 (8.3%)	1	0/14 (0%)	0	1/26 (3.8%)	1	1/64 (1.6%)	1
Reproductive system and breast disorders
Dysmenorrhoea	0/12 (0%)	0	3/26 (11.5%)	3	3/38 (7.9%)	3	0/12 (0%)	0	0/14 (0%)	0	0/26 (0%)	0	3/64 (4.7%)	3
Pruritus genital	0/12 (0%)	0	0/26 (0%)	0	0/38 (0%)	0	1/12 (8.3%)	1	0/14 (0%)	0	1/26 (3.8%)	1	1/64 (1.6%)	1
Vaginal discharge	0/12 (0%)	0	2/26 (7.7%)	2	2/38 (5.3%)	2	0/12 (0%)	0	0/14 (0%)	0	0/26 (0%)	0	2/64 (3.1%)	2
Respiratory, thoracic and mediastinal disorders
Cough	0/12 (0%)	0	0/26 (0%)	0	0/38 (0%)	0	2/12 (16.7%)	2	2/14 (14.3%)	2	4/26 (15.4%)	4	4/64 (6.3%)	4
Epistaxis	0/12 (0%)	0	1/26 (3.8%)	3	1/38 (2.6%)	3	1/12 (8.3%)	1	0/14 (0%)	0	1/26 (3.8%)	1	2/64 (3.1%)	4
Nasal congestion	0/12 (0%)	0	0/26 (0%)	0	0/38 (0%)	0	1/12 (8.3%)	1	0/14 (0%)	0	1/26 (3.8%)	1	1/64 (1.6%)	1
Oropharyngeal pain	2/12 (16.7%)	2	1/26 (3.8%)	1	3/38 (7.9%)	3	0/12 (0%)	0	0/14 (0%)	0	0/26 (0%)	0	3/64 (4.7%)	3
Rhinorrhoea	0/12 (0%)	0	0/26 (0%)	0	0/38 (0%)	0	2/12 (16.7%)	2	0/14 (0%)	0	2/26 (7.7%)	2	2/64 (3.1%)	2
Sneezing	0/12 (0%)	0	0/26 (0%)	0	0/38 (0%)	0	1/12 (8.3%)	1	0/14 (0%)	0	1/26 (3.8%)	1	1/64 (1.6%)	1
Skin and subcutaneous tissue disorders
Eczema	1/12 (8.3%)	1	0/26 (0%)	0	1/38 (2.6%)	1	0/12 (0%)	0	0/14 (0%)	0	0/26 (0%)	0	1/64 (1.6%)	1
Pruritus	1/12 (8.3%)	1	4/26 (15.4%)	4	5/38 (13.2%)	5	1/12 (8.3%)	1	1/14 (7.1%)	1	2/26 (7.7%)	2	7/64 (10.9%)	7
Rash	1/12 (8.3%)	1	0/26 (0%)	0	1/38 (2.6%)	1	1/12 (8.3%)	1	0/14 (0%)	0	1/26 (3.8%)	1	2/64 (3.1%)	2
Rash papular	1/12 (8.3%)	1	0/26 (0%)	0	1/38 (2.6%)	1	0/12 (0%)	0	0/14 (0%)	0	0/26 (0%)	0	1/64 (1.6%)	1

Limitations/Caveats

[Not Specified]

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Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

AbbVie requests that any investigator or institution that plans on presenting/publishing results disclosure, provide written notification of their request 60 days prior to their presentation/publication. AbbVie requests that no presentation/publication will be instituted until 12 months after a study is completed, or after the first presentation/publication whichever occurs first. A delay may be proposed of a presentation/publication if AbbVie needs to secure patent or proprietary protection.